{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:15:16Z","timestamp":1784175316791,"version":"3.55.0"},"reference-count":107,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Circulatory iron is a hazardous biometal. Therefore, iron is transported in a redox-safe state by a serum glycoprotein - transferrin (<jats:bold>TF<\/jats:bold>). Different organs acquire iron from the systemic circulation through a tightly regulated mechanism at the blood-tissue interface which involves receptor-mediated internalization of TF. Thus, abnormal TF trafficking may lead to iron dyshomeostasis associated with several diseases including neurodegeneration. Iron -induced toxicity can cause neuronal damage to iron-sensitive brain regions. Recently, it was discovered that CAMKK2, a calcium (Ca<jats:sup>2+<\/jats:sup>)\/calmodulin-activated kinase, controls receptor-mediated TF trafficking in mouse tissues, specifically in the brain. The biological function of CAMKK2 is mediated through multiple downstream effectors. Both CAMKK2 and one of its downstream kinase, CAMK4, exhibit overlapping expression in mouse brain. The role of CAMK4 in vesicular transport has been reported and loss of CAMKK2 or CAMK4 leads to cognitive defects in mouse. Therefore, it was hypothesized that CAMKK2-CAMK4 signaling regulates receptor-mediated TF trafficking and iron homeostasis which may be responsible for the neuronal malfunction observed in CAMKK2- or CAMK4-deficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CAMK4<jats:sup>\u2212\/\u2212<\/jats:sup>mouse was used to study tissue-specific turnover of TF, TF-receptor (<jats:bold>TFRC<\/jats:bold>) and iron. CRISPR\/Cas9-based CAMKK2 and\/or CAMK4 deleted human embryonic kidney-derived HEK293 cell clones were used to study the molecular defects in receptor-mediated TF trafficking. Further, a \u201czero functional G protein\u201d condition in HEK293 cell was exploited to study CAMKK2-CAMK4 signaling-mediated regulation of intracellular Ca<jats:sup>2+<\/jats:sup>homeostasis which was linked to calcium signaling during TF trafficking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Loss of CAMK4 leads to abnormal post-translational modifications (<jats:bold>PTMs<\/jats:bold>) and turnover of TF in mouse cerebellum and liver which was associated with iron dyshomeostasis in these tissues. The HEK293 cell-based study revealed that the absence of CAMKK2-CAMK4 signaling altered intracellular Ca<jats:sup>2+<\/jats:sup>homeostasis and lead to abnormal calcium signaling during TF trafficking. Also, CAMKK2-CAMK4 signaling deficiency affected the molecular interaction of TF and TF-receptor-associated protein complexes which indicated a potential failure in the recruitment of interacting proteins due to differential PTMs in TF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, this study established a novel mechanistic link between intracellular Ca<jats:sup>2+<\/jats:sup>\u00a0level, receptor-mediated TF trafficking, and iron homeostasis, all regulated by CAMKK2-CAMK4 signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Graphical abstract<\/jats:title><\/jats:sec>","DOI":"10.1186\/s12964-020-00575-0","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T09:02:48Z","timestamp":1590570168000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["CAMKK2-CAMK4 signaling regulates transferrin trafficking, turnover, and iron\u00a0homeostasis"],"prefix":"10.1186","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0943-2542","authenticated-orcid":false,"given":"Mohammad Golam","family":"Sabbir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"issue":"8","key":"575_CR1","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nrn3453","volume":"14","author":"TA Rouault","year":"2013","unstructured":"Rouault TA. Iron metabolism in the CNS: implications for neurodegenerative diseases. Nat Rev Neurosci. 2013;14(8):551\u201364.","journal-title":"Nat Rev Neurosci"},{"issue":"4","key":"575_CR2","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S1359-6446(04)03333-1","volume":"10","author":"PT Gomme","year":"2005","unstructured":"Gomme PT, McCann KB, Bertolini J. Transferrin: structure, function and potential therapeutic actions. Drug Discov Today. 2005;10(4):267\u201373.","journal-title":"Drug Discov Today"},{"issue":"18","key":"575_CR3","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1089\/ars.2011.4271","volume":"18","author":"A Lawen","year":"2013","unstructured":"Lawen A, Lane DJ. Mammalian iron homeostasis in health and disease: uptake, storage, transport, and molecular mechanisms of action. Antioxid Redox Signal. 2013;18(18):2473\u2013507.","journal-title":"Antioxid Redox Signal"},{"issue":"1","key":"575_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0304-4157(96)00014-7","volume":"1331","author":"DR Richardson","year":"1997","unstructured":"Richardson DR, Ponka P. The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochim Biophys Acta. 1997;1331(1):1\u201340.","journal-title":"Biochim Biophys Acta"},{"issue":"12","key":"575_CR5","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1093\/nar\/23.12.2206","volume":"23","author":"BE Sawaya","year":"1995","unstructured":"Sawaya BE, Schaeffer E. Transcription of the human transferrin gene in neuronal cells. Nucleic Acids Res. 1995;23(12):2206\u201311.","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"575_CR6","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1016\/j.bbamcr.2015.01.021","volume":"1853","author":"DJ Lane","year":"2015","unstructured":"Lane DJ, et al. Cellular iron uptake, trafficking and metabolism: Key molecules and mechanisms and their roles in disease. Biochim Biophys Acta. 2015;1853(5):1130\u201344.","journal-title":"Biochim Biophys Acta"},{"issue":"6","key":"575_CR7","first-page":"690","volume":"110","author":"SE Bernstein","year":"1987","unstructured":"Bernstein SE. Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia. J Lab Clin Med. 1987;110(6):690\u2013705.","journal-title":"J Lab Clin Med"},{"issue":"3","key":"575_CR8","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1182\/blood.V96.3.1113","volume":"96","author":"CC Trenor 3rd","year":"2000","unstructured":"Trenor CC 3rd, et al. The molecular defect in hypotransferrinemic mice. Blood. 2000;96(3):1113\u20138.","journal-title":"Blood"},{"key":"575_CR9","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3389\/fmolb.2018.00099","volume":"5","author":"MG Sabbir","year":"2018","unstructured":"Sabbir MG. Loss of Ca(2+)\/Calmodulin Dependent Protein Kinase Kinase 2 Leads to Aberrant Transferrin Phosphorylation and Trafficking: A Potential Biomarker for Alzheimer's Disease. Front Mol Biosci. 2018;5:99.","journal-title":"Front Mol Biosci"},{"issue":"42","key":"575_CR10","doi-asserted-by":"publisher","first-page":"12823","DOI":"10.1021\/bi971348i","volume":"36","author":"H Tokumitsu","year":"1997","unstructured":"Tokumitsu H, et al. Calcium\/calmodulin-dependent protein kinase kinase: identification of regulatory domains. Biochemistry. 1997;36(42):12823\u20137.","journal-title":"Biochemistry"},{"issue":"Suppl 1","key":"575_CR11","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/j.1471-4159.2011.07507.x","volume":"120","author":"A Fisher","year":"2012","unstructured":"Fisher A. Cholinergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: perspectives and challenges in treatment of Alzheimer's disease. J Neurochem. 2012;120(Suppl 1):22\u201333.","journal-title":"J Neurochem"},{"key":"575_CR12","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.phrs.2015.03.010","volume":"97","author":"M Golpich","year":"2015","unstructured":"Golpich M, et al. Glycogen synthase kinase-3 beta (GSK-3beta) signaling: Implications for Parkinson's disease. Pharmacol Res. 2015;97:16\u201326.","journal-title":"Pharmacol Res"},{"issue":"2","key":"575_CR13","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1021\/cn300182g","volume":"4","author":"JA Morales-Garcia","year":"2013","unstructured":"Morales-Garcia JA, et al. Glycogen synthase kinase-3 inhibitors as potent therapeutic agents for the treatment of Parkinson disease. ACS Chem Neurosci. 2013;4(2):350\u201360.","journal-title":"ACS Chem Neurosci"},{"issue":"1","key":"575_CR14","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1080\/17425255.2018.1417387","volume":"14","author":"H Choi","year":"2018","unstructured":"Choi H, Koh SH. Understanding the role of glycogen synthase kinase-3 in L-DOPA-induced dyskinesia in Parkinson's disease. Expert Opin Drug Metab Toxicol. 2018;14(1):83\u201390.","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"575_CR15","first-page":"46","volume":"7","author":"M Llorens-Martin","year":"2014","unstructured":"Llorens-Martin M, et al. GSK-3beta, a pivotal kinase in Alzheimer disease. Front Mol Neurosci. 2014;7:46.","journal-title":"Front Mol Neurosci"},{"issue":"6","key":"575_CR16","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1111\/j.1471-4159.2007.05194.x","volume":"104","author":"C Hooper","year":"2008","unstructured":"Hooper C, Killick R, Lovestone S. The GSK3 hypothesis of Alzheimer's disease. J Neurochem. 2008;104(6):1433\u20139.","journal-title":"J Neurochem"},{"key":"575_CR17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3389\/fnmol.2011.00017","volume":"4","author":"A Kremer","year":"2011","unstructured":"Kremer A, et al. GSK3 and Alzheimer's Disease: Facts and Fiction. Front Mol Neurosci. 2011;4:17.","journal-title":"Front Mol Neurosci"},{"issue":"3","key":"575_CR18","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.tcb.2011.11.003","volume":"22","author":"ZH Cheung","year":"2012","unstructured":"Cheung ZH, Ip NY. Cdk5: a multifaceted kinase in neurodegenerative diseases. Trends Cell Biol. 2012;22(3):169\u201375.","journal-title":"Trends Cell Biol"},{"issue":"5","key":"575_CR19","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1111\/dgd.12138","volume":"56","author":"T Kawauchi","year":"2014","unstructured":"Kawauchi T. Cdk5 regulates multiple cellular events in neural development, function and disease. Develop Growth Differ. 2014;56(5):335\u201348.","journal-title":"Develop Growth Differ"},{"issue":"32","key":"575_CR20","doi-asserted-by":"publisher","first-page":"28066","DOI":"10.1074\/jbc.M111.251504","volume":"286","author":"MF Green","year":"2011","unstructured":"Green MF, et al. Ca2+\/Calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation. J Biol Chem. 2011;286(32):28066\u201379.","journal-title":"J Biol Chem"},{"issue":"38","key":"575_CR21","doi-asserted-by":"publisher","first-page":"31658","DOI":"10.1074\/jbc.R112.356485","volume":"287","author":"L Racioppi","year":"2012","unstructured":"Racioppi L, Means AR. Calcium\/calmodulin-dependent protein kinase kinase 2: roles in signaling and pathophysiology. J Biol Chem. 2012;287(38):31658\u201365.","journal-title":"J Biol Chem"},{"key":"575_CR22","doi-asserted-by":"crossref","unstructured":"Wang, Y., Y. Shi, and H. Wei, Calcium Dysregulation in Alzheimer's Disease: A Target for New Drug Development. J Alzheimers Dis Parkinsonism. 2017;7(5):1\u201315.","DOI":"10.4172\/2161-0460.1000374"},{"key":"575_CR23","doi-asserted-by":"publisher","first-page":"180","DOI":"10.3389\/fnins.2019.00180","volume":"13","author":"A Ndayisaba","year":"2019","unstructured":"Ndayisaba A, Kaindlstorfer C, Wenning GK. Iron in Neurodegeneration - Cause or Consequence? Front Neurosci. 2019;13:180.","journal-title":"Front Neurosci"},{"issue":"1","key":"575_CR24","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0730-725X(96)00234-2","volume":"15","author":"G Bartzokis","year":"1997","unstructured":"Bartzokis G, et al. MR evaluation of age-related increase of brain iron in young adult and older normal males. Magn Reson Imaging. 1997;15(1):29\u201335.","journal-title":"Magn Reson Imaging"},{"issue":"4","key":"575_CR25","doi-asserted-by":"publisher","first-page":"879","DOI":"10.3233\/JAD-2009-1010","volume":"16","author":"S Altamura","year":"2009","unstructured":"Altamura S, Muckenthaler MU. Iron toxicity in diseases of aging: Alzheimer's disease, Parkinson's disease and atherosclerosis. J Alzheimers Dis. 2009;16(4):879\u201395.","journal-title":"J Alzheimers Dis"},{"issue":"30","key":"575_CR26","doi-asserted-by":"publisher","first-page":"9752","DOI":"10.1523\/JNEUROSCI.23-30-09752.2003","volume":"23","author":"M Peters","year":"2003","unstructured":"Peters M, et al. Loss of Ca2+\/calmodulin kinase kinase beta affects the formation of some, but not all, types of hippocampus-dependent long-term memory. J Neurosci. 2003;23(30):9752\u201360.","journal-title":"J Neurosci"},{"issue":"10","key":"575_CR27","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1016\/j.tem.2016.06.001","volume":"27","author":"KL Marcelo","year":"2016","unstructured":"Marcelo KL, Means AR, York B. The Ca(2+)\/Calmodulin\/CaMKK2 Axis: Nature's Metabolic CaMshaft. Trends Endocrinol Metab. 2016;27(10):706\u201318.","journal-title":"Trends Endocrinol Metab"},{"issue":"15","key":"575_CR28","doi-asserted-by":"publisher","first-page":"3786","DOI":"10.1523\/JNEUROSCI.3294-03.2004","volume":"24","author":"GA Wayman","year":"2004","unstructured":"Wayman GA, et al. Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I. J Neurosci. 2004;24(15):3786\u201394.","journal-title":"J Neurosci"},{"issue":"15","key":"575_CR29","doi-asserted-by":"publisher","first-page":"15411","DOI":"10.1074\/jbc.M312543200","volume":"279","author":"CR Kahl","year":"2004","unstructured":"Kahl CR, Means AR. Regulation of cyclin D1\/Cdk4 complexes by calcium\/calmodulin-dependent protein kinase I. J Biol Chem. 2004;279(15):15411\u20139.","journal-title":"J Biol Chem"},{"issue":"5","key":"575_CR30","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.cmet.2008.02.011","volume":"7","author":"KA Anderson","year":"2008","unstructured":"Anderson KA, et al. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab. 2008;7(5):377\u201388.","journal-title":"Cell Metab"},{"issue":"2","key":"575_CR31","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1210\/me.2011-1299","volume":"26","author":"KA Anderson","year":"2012","unstructured":"Anderson KA, et al. Deletion of CaMKK2 from the liver lowers blood glucose and improves whole-body glucose tolerance in the mouse. Mol Endocrinol. 2012;26(2):281\u201391.","journal-title":"Mol Endocrinol"},{"issue":"10","key":"575_CR32","doi-asserted-by":"publisher","first-page":"3668","DOI":"10.1210\/en.2011-1107","volume":"152","author":"F Lin","year":"2011","unstructured":"Lin F, Ribar TJ, Means AR. The Ca2+\/calmodulin-dependent protein kinase kinase, CaMKK2, inhibits preadipocyte differentiation. Endocrinology. 2011;152(10):3668\u201379.","journal-title":"Endocrinology"},{"issue":"2","key":"575_CR33","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1002\/hep.27832","volume":"62","author":"F Lin","year":"2015","unstructured":"Lin F, et al. The camKK2\/camKIV relay is an essential regulator of hepatic cancer. Hepatology. 2015;62(2):505\u201320.","journal-title":"Hepatology"},{"issue":"20","key":"575_CR34","doi-asserted-by":"publisher","first-page":"2330","DOI":"10.1101\/gad.1977210","volume":"24","author":"F Oury","year":"2010","unstructured":"Oury F, et al. CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neurons. Genes Dev. 2010;24(20):2330\u201342.","journal-title":"Genes Dev"},{"issue":"7047","key":"575_CR35","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/nature03571","volume":"436","author":"L Pelkmans","year":"2005","unstructured":"Pelkmans L, et al. Genome-wide analysis of human kinases in clathrin- and caveolae\/raft-mediated endocytosis. Nature. 2005;436(7047):78\u201386.","journal-title":"Nature"},{"issue":"5","key":"575_CR36","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/nn0504-483","volume":"7","author":"N Heintz","year":"2004","unstructured":"Heintz N. Gene Expression Nervous System Atlas (GENSAT). Nat Neurosci. 2004;7(5):483.","journal-title":"Nat Neurosci"},{"issue":"4","key":"575_CR37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040086","volume":"4","author":"S Magdaleno","year":"2006","unstructured":"Magdaleno S, et al. BGEM: an in situ hybridization database of gene expression in the embryonic and adult mouse nervous system. PLoS Biol. 2006;4(4):e86.","journal-title":"PLoS Biol"},{"issue":"1","key":"575_CR38","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/s41467-017-02661-3","volume":"9","author":"M Grundmann","year":"2018","unstructured":"Grundmann M, et al. Lack of beta-arrestin signaling in the absence of active G proteins. Nat Commun. 2018;9(1):341.","journal-title":"Nat Commun"},{"issue":"4","key":"575_CR39","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/78153","volume":"25","author":"JY Wu","year":"2000","unstructured":"Wu JY, et al. Spermiogenesis and exchange of basic nuclear proteins are impaired in male germ cells lacking Camk4. Nat Genet. 2000;25(4):448\u201352.","journal-title":"Nat Genet"},{"key":"575_CR40","doi-asserted-by":"publisher","first-page":"105376","DOI":"10.1016\/j.jsbmb.2019.105376","volume":"191","author":"MG Sabbir","year":"2019","unstructured":"Sabbir MG. Progesterone induced Warburg effect in HEK293 cells is associated with post-translational modifications and proteasomal degradation of progesterone receptor membrane component 1. J Steroid Biochem Mol Biol. 2019;191:105376.","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"3 Suppl","key":"575_CR41","first-page":"S53","volume":"21","author":"V Thulasiraman","year":"2010","unstructured":"Thulasiraman V, Waker J II, Berkelman T. Evaluation of Oriole Fluorescent Gel Stain and Comparison to SYPRO Ruby. Journal of Biomolecular Techniques : JBT. 2010;21(3 Suppl):S53.","journal-title":"Journal of Biomolecular Techniques : JBT"},{"key":"575_CR42","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jbior.2016.05.001","volume":"62","author":"S Bahrami","year":"2016","unstructured":"Bahrami S, Drablos F. Gene regulation in the immediate-early response process. Adv Biol Regul. 2016;62:37\u201349.","journal-title":"Adv Biol Regul"},{"key":"575_CR43","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3389\/fnins.2018.00402","volume":"12","author":"MG Sabbir","year":"2018","unstructured":"Sabbir MG, Calcutt NA, Fernyhough P. Muscarinic Acetylcholine Type 1 Receptor Activity Constrains Neurite Outgrowth by Inhibiting Microtubule Polymerization and Mitochondrial Trafficking in Adult Sensory Neurons. Front Neurosci. 2018;12:402.","journal-title":"Front Neurosci"},{"key":"575_CR44","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.neuropharm.2018.09.020","volume":"143","author":"MG Sabbir","year":"2018","unstructured":"Sabbir MG, Fernyhough P. Muscarinic receptor antagonists activate ERK-CREB signaling to augment neurite outgrowth of adult sensory neurons. Neuropharmacology. 2018;143:268\u201381.","journal-title":"Neuropharmacology"},{"issue":"7","key":"575_CR45","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1021\/ac60289a016","volume":"42","author":"LL Stookey","year":"1970","unstructured":"Stookey LL. Ferrozine---a new spectrophotometric reagent for iron. Anal Chem. 1970;42(7):779\u201381.","journal-title":"Anal Chem"},{"issue":"17","key":"575_CR46","doi-asserted-by":"publisher","first-page":"12900","DOI":"10.1074\/jbc.275.17.12900","volume":"275","author":"SJ Mundell","year":"2000","unstructured":"Mundell SJ, Benovic JL. Selective regulation of endogenous G protein-coupled receptors by arrestins in HEK293 cells. J Biol Chem. 2000;275(17):12900\u20138.","journal-title":"J Biol Chem"},{"issue":"46","key":"575_CR47","doi-asserted-by":"publisher","first-page":"39726","DOI":"10.1074\/jbc.M111.289546","volume":"286","author":"GP Hussmann","year":"2011","unstructured":"Hussmann GP, et al. Endogenously expressed muscarinic receptors in HEK293 cells augment up-regulation of stably expressed alpha4beta2 nicotinic receptors. J Biol Chem. 2011;286(46):39726\u201337.","journal-title":"J Biol Chem"},{"issue":"3","key":"575_CR48","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1093\/oxfordjournals.jbchem.a021780","volume":"122","author":"T Maruyama","year":"1997","unstructured":"Maruyama T, et al. 2APB, 2-aminoethoxydiphenyl borate, a membrane-penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release. J Biochem. 1997;122(3):498\u2013505.","journal-title":"J Biochem"},{"issue":"7","key":"575_CR49","doi-asserted-by":"publisher","first-page":"817","DOI":"10.4155\/fmc-2016-0024","volume":"8","author":"C Tian","year":"2016","unstructured":"Tian C, et al. Store-operated CRAC channel inhibitors: opportunities and challenges. Future Med Chem. 2016;8(7):817\u201332.","journal-title":"Future Med Chem"},{"issue":"3","key":"575_CR50","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1080\/00401706.1964.10490181","volume":"6","author":"OJ Dunn","year":"1964","unstructured":"Dunn OJ. Multiple Comparisons Using Rank Sums. Technometrics. 1964;6(3):241\u201352.","journal-title":"Technometrics"},{"key":"575_CR51","unstructured":"Siegel, S., ed. Nonparametric statistics for the behavioral sciences. McGraw-Hill series in psychology. 1956, McGraw-Hill: New York 312."},{"issue":"33","key":"575_CR52","doi-asserted-by":"publisher","first-page":"31113","DOI":"10.1074\/jbc.M011720200","volume":"276","author":"LS Hsu","year":"2001","unstructured":"Hsu LS, et al. Human Ca2+\/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity. J Biol Chem. 2001;276(33):31113\u201323.","journal-title":"J Biol Chem"},{"issue":"6","key":"575_CR53","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.4161\/rna.8.6.16691","volume":"8","author":"W Cao","year":"2011","unstructured":"Cao W, et al. Differential effects of PKA-controlled CaMKK2 variants on neuronal differentiation. RNA Biol. 2011;8(6):1061\u201372.","journal-title":"RNA Biol"},{"issue":"Database issue","key":"575_CR54","doi-asserted-by":"publisher","first-page":"D512","DOI":"10.1093\/nar\/gku1267","volume":"43","author":"PV Hornbeck","year":"2015","unstructured":"Hornbeck PV, et al. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 2015;43(Database issue):D512\u201320.","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"575_CR55","doi-asserted-by":"publisher","first-page":"D261","DOI":"10.1093\/nar\/gkr1122","volume":"40","author":"PV Hornbeck","year":"2012","unstructured":"Hornbeck PV, et al. PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse. Nucleic Acids Res. 2012;40(Database issue):D261\u201370.","journal-title":"Nucleic Acids Res"},{"key":"575_CR56","first-page":"531","volume":"112","author":"MR Wilkins","year":"1999","unstructured":"Wilkins MR, et al. Protein identification and analysis tools in the ExPASy server. Methods Mol Biol. 1999;112:531\u201352.","journal-title":"Methods Mol Biol"},{"issue":"5","key":"575_CR57","doi-asserted-by":"publisher","first-page":"247","DOI":"10.4161\/bbug.2.5.17844","volume":"2","author":"S Dwane","year":"2011","unstructured":"Dwane S, Kiely PA. Tools used to study how protein complexes are assembled in signaling cascades. Bioeng Bugs. 2011;2(5):247\u201359.","journal-title":"Bioeng Bugs"},{"issue":"23","key":"575_CR58","doi-asserted-by":"publisher","first-page":"5214","DOI":"10.1002\/pmic.200900151","volume":"9","author":"I Wittig","year":"2009","unstructured":"Wittig I, Schagger H. Native electrophoretic techniques to identify protein-protein interactions. Proteomics. 2009;9(23):5214\u201323.","journal-title":"Proteomics"},{"issue":"21","key":"575_CR59","doi-asserted-by":"publisher","first-page":"3603","DOI":"10.1002\/pmic.201500045","volume":"15","author":"N Munawar","year":"2015","unstructured":"Munawar N, et al. Native gel analysis of macromolecular protein complexes in cultured mammalian cells. Proteomics. 2015;15(21):3603\u201312.","journal-title":"Proteomics"},{"issue":"3","key":"575_CR60","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1021\/ja01207a034","volume":"68","author":"EJ Cohn","year":"1946","unstructured":"Cohn EJ, et al. Preparation and Properties of Serum and Plasma Proteins. IV. A System for the Separation into Fractions of the Protein and Lipoprotein Components of Biological Tissues and Fluids1a,b,c,d. J Am Chem Soc. 1946;68(3):459\u201375.","journal-title":"J Am Chem Soc"},{"key":"575_CR61","doi-asserted-by":"crossref","unstructured":"Qian, S., et al., Quantitative Analysis of Ubiquitinated Proteins in Human Pituitary and Pituitary Adenoma Tissues. Front Endocrinol. 2019;10(328):1\u201322.","DOI":"10.3389\/fendo.2019.00328"},{"issue":"9","key":"575_CR62","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1021\/ac048494w","volume":"77","author":"K Zhu","year":"2005","unstructured":"Zhu K, et al. Protein pI Shifts due to Posttranslational Modifications in the Separation and Characterization of Proteins. Anal Chem. 2005;77(9):2745\u201355.","journal-title":"Anal Chem"},{"issue":"3","key":"575_CR63","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1083\/jcb.103.3.851","volume":"103","author":"B Iacopetta","year":"1986","unstructured":"Iacopetta B, et al. Role of intracellular calcium and protein kinase C in the endocytosis of transferrin and insulin by HL60 cells. J Cell Biol. 1986;103(3):851\u20136.","journal-title":"J Cell Biol"},{"issue":"4","key":"575_CR64","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1083\/jcb.108.4.1245","volume":"108","author":"CJ Beckers","year":"1989","unstructured":"Beckers CJ, Balch WE. Calcium and GTP: essential components in vesicular trafficking between the endoplasmic reticulum and Golgi apparatus. J Cell Biol. 1989;108(4):1245\u201356.","journal-title":"J Cell Biol"},{"issue":"3","key":"575_CR65","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1111\/j.1432-1033.1997.00689.x","volume":"250","author":"J Sainte-Marie","year":"1997","unstructured":"Sainte-Marie J, et al. Transferrin receptor functions as a signal-transduction molecule for its own recycling via increases in the internal Ca2+ concentration. Eur J Biochem. 1997;250(3):689\u201397.","journal-title":"Eur J Biochem"},{"issue":"2","key":"575_CR66","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/0006-8993(86)90576-7","volume":"368","author":"JR Connor","year":"1986","unstructured":"Connor JR, Fine RE. The distribution of transferrin immunoreactivity in the rat central nervous system. Brain Res. 1986;368(2):319\u201328.","journal-title":"Brain Res"},{"issue":"11","key":"575_CR67","doi-asserted-by":"crossref","first-page":"5293","DOI":"10.1016\/S0021-9258(18)61187-1","volume":"262","author":"AR Aldred","year":"1987","unstructured":"Aldred AR, et al. Distribution of transferrin synthesis in brain and other tissues in the rat. J Biol Chem. 1987;262(11):5293\u20137.","journal-title":"J Biol Chem"},{"issue":"11","key":"575_CR68","doi-asserted-by":"publisher","first-page":"3723","DOI":"10.1073\/pnas.83.11.3723","volume":"83","author":"RL Idzerda","year":"1986","unstructured":"Idzerda RL, et al. Rat transferrin gene expression: tissue-specific regulation by iron deficiency. Proc Natl Acad Sci U S A. 1986;83(11):3723\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"575_CR69","doi-asserted-by":"crossref","unstructured":"Espinosa de los Monteros, A., et al., Brain-specific expression of the human transferrin gene. Similar elements govern transcription in oligodendrocytes and in a neuronal cell line. J Biol Chem, 1994. 269(39): p. 24504\u201324510.","DOI":"10.1016\/S0021-9258(19)51112-7"},{"issue":"3","key":"575_CR70","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/mrd.20080","volume":"68","author":"MA Saxlund","year":"2004","unstructured":"Saxlund MA, Sadler-Riggleman I, Skinner MK. Role of basic helix-loop-helix (bHLH) and CREB transcription factors in the regulation of Sertoli cell androgen-binding protein expression. Mol Reprod Dev. 2004;68(3):269\u201378.","journal-title":"Mol Reprod Dev"},{"issue":"31","key":"575_CR71","doi-asserted-by":"publisher","first-page":"24185","DOI":"10.1074\/jbc.M000944200","volume":"275","author":"CN Lok","year":"2000","unstructured":"Lok CN, Ponka P. Identification of an erythroid active element in the transferrin receptor gene. J Biol Chem. 2000;275(31):24185\u201390.","journal-title":"J Biol Chem"},{"issue":"26","key":"575_CR72","doi-asserted-by":"publisher","first-page":"24044","DOI":"10.1074\/jbc.M100247200","volume":"276","author":"J Kasahara","year":"2001","unstructured":"Kasahara J, Fukunaga K, Miyamoto E. Activation of calcium\/calmodulin-dependent protein kinase IV in long term potentiation in the rat hippocampal CA1 region. J Biol Chem. 2001;276(26):24044\u201350.","journal-title":"J Biol Chem"},{"key":"575_CR73","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/S0079-6468(05)43004-0","volume":"43","author":"RM Eglen","year":"2005","unstructured":"Eglen RM. Muscarinic receptor subtype pharmacology and physiology. Prog Med Chem. 2005;43:105\u201336.","journal-title":"Prog Med Chem"},{"issue":"7","key":"575_CR74","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/nrd4295","volume":"13","author":"AC Kruse","year":"2014","unstructured":"Kruse AC, et al. Muscarinic acetylcholine receptors: novel opportunities for drug development. Nat Rev Drug Discov. 2014;13(7):549\u201360.","journal-title":"Nat Rev Drug Discov"},{"issue":"9","key":"575_CR75","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/nrd2379","volume":"6","author":"J Wess","year":"2007","unstructured":"Wess J, Eglen RM, Gautam D. Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nat Rev Drug Discov. 2007;6(9):721\u201333.","journal-title":"Nat Rev Drug Discov"},{"issue":"2","key":"575_CR76","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1124\/pr.109.002436","volume":"62","author":"LM Luttrell","year":"2010","unstructured":"Luttrell LM, Gesty-Palmer D. Beyond desensitization: physiological relevance of arrestin-dependent signaling. Pharmacol Rev. 2010;62(2):305\u201330.","journal-title":"Pharmacol Rev"},{"issue":"4","key":"575_CR77","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1080\/10606820308263","volume":"9","author":"AA Lanzafame","year":"2003","unstructured":"Lanzafame AA, Christopoulos A, Mitchelson F. Cellular signaling mechanisms for muscarinic acetylcholine receptors. Receptors Channels. 2003;9(4):241\u201360.","journal-title":"Receptors Channels"},{"issue":"6","key":"575_CR78","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1124\/mol.114.096008","volume":"87","author":"J Proft","year":"2015","unstructured":"Proft J, Weiss N. G protein regulation of neuronal calcium channels: back to the future. Mol Pharmacol. 2015;87(6):890\u2013906.","journal-title":"Mol Pharmacol"},{"issue":"7","key":"575_CR79","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1016\/j.bbamem.2012.10.004","volume":"1828","author":"GW Zamponi","year":"2013","unstructured":"Zamponi GW, Currie KP. Regulation of Ca(V)2 calcium channels by G protein coupled receptors. Biochim Biophys Acta. 2013;1828(7):1629\u201343.","journal-title":"Biochim Biophys Acta"},{"key":"575_CR80","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3389\/fonc.2017.00140","volume":"7","author":"E Kania","year":"2017","unstructured":"Kania E, et al. IP3 Receptor-Mediated Calcium Signaling and Its Role in Autophagy in Cancer. Front Oncol. 2017;7:140.","journal-title":"Front Oncol"},{"issue":"1","key":"575_CR81","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1038\/s41467-018-02868-y","volume":"9","author":"A Keshelava","year":"2018","unstructured":"Keshelava A, et al. High capacity in G protein-coupled receptor signaling. Nat Commun. 2018;9(1):876.","journal-title":"Nat Commun"},{"issue":"7","key":"575_CR82","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1177\/2472555217693378","volume":"22","author":"RK Gupta","year":"2017","unstructured":"Gupta RK, et al. Comparison of Calcium Dynamics and Specific Features for G Protein-Coupled Receptor-Targeting Drugs Using Live Cell Imaging and Automated Analysis. SLAS Discov. 2017;22(7):848\u201358.","journal-title":"SLAS Discov"},{"key":"575_CR83","doi-asserted-by":"publisher","first-page":"14335","DOI":"10.1038\/ncomms14335","volume":"8","author":"CH Liu","year":"2017","unstructured":"Liu CH, et al. Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling. Nat Commun. 2017;8:14335.","journal-title":"Nat Commun"},{"issue":"2","key":"575_CR84","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1111\/j.1471-4159.2010.06626.x","volume":"113","author":"XP Dong","year":"2010","unstructured":"Dong XP, Wang X, Xu H. TRP channels of intracellular membranes. J Neurochem. 2010;113(2):313\u201328.","journal-title":"J Neurochem"},{"issue":"6","key":"575_CR85","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1038\/sj.bjp.0707675","volume":"153","author":"K Togashi","year":"2008","unstructured":"Togashi K, Inada H, Tominaga M. Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB). Br J Pharmacol. 2008;153(6):1324\u201330.","journal-title":"Br J Pharmacol"},{"issue":"4","key":"575_CR86","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/sj.bjp.0706197","volume":"145","author":"SZ Xu","year":"2005","unstructured":"Xu SZ, et al. Block of TRPC5 channels by 2-aminoethoxydiphenyl borate: a differential, extracellular and voltage-dependent effect. Br J Pharmacol. 2005;145(4):405\u201314.","journal-title":"Br J Pharmacol"},{"issue":"3","key":"575_CR87","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/sj.embor.7400921","volume":"8","author":"JC Hay","year":"2007","unstructured":"Hay JC. Calcium: a fundamental regulator of intracellular membrane fusion? EMBO Rep. 2007;8(3):236\u201340.","journal-title":"EMBO Rep"},{"issue":"22","key":"575_CR88","doi-asserted-by":"publisher","first-page":"20083","DOI":"10.1074\/jbc.M301642200","volume":"278","author":"A Savina","year":"2003","unstructured":"Savina A, et al. Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J Biol Chem. 2003;278(22):20083\u201390.","journal-title":"J Biol Chem"},{"issue":"4","key":"575_CR89","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1034\/j.1600-0854.2002.030407.x","volume":"3","author":"DE Knight","year":"2002","unstructured":"Knight DE. Calcium-dependent transferrin receptor recycling in bovine chromaffin cells. Traffic. 2002;3(4):298\u2013307.","journal-title":"Traffic"},{"issue":"4","key":"575_CR90","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/S0092-8674(04)00130-8","volume":"116","author":"Y Cheng","year":"2004","unstructured":"Cheng Y, et al. Structure of the human transferrin receptor-transferrin complex. Cell. 2004;116(4):565\u201376.","journal-title":"Cell"},{"issue":"8","key":"575_CR91","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1002\/j.1460-2075.1989.tb08347.x","volume":"8","author":"E Alvarez","year":"1989","unstructured":"Alvarez E, Girones N, Davis RJ. Intermolecular disulfide bonds are not required for the expression of the dimeric state and functional activity of the transferrin receptor. EMBO J. 1989;8(8):2231\u201340.","journal-title":"EMBO J"},{"issue":"1","key":"575_CR92","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ab.2010.05.011","volume":"405","author":"BY Lu","year":"2010","unstructured":"Lu BY, Chang JY. Rapid and irreversible reduction of protein disulfide bonds. Anal Biochem. 2010;405(1):67\u201372.","journal-title":"Anal Biochem"},{"issue":"12","key":"575_CR93","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1074\/mcp.M112.017905","volume":"11","author":"SA Wagner","year":"2012","unstructured":"Wagner SA, et al. Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues. Mol Cell Proteomics. 2012;11(12):1578\u201385.","journal-title":"Mol Cell Proteomics"},{"issue":"7","key":"575_CR94","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/s41594-018-0084-y","volume":"25","author":"V Akimov","year":"2018","unstructured":"Akimov V, et al. UbiSite approach for comprehensive mapping of lysine and N-terminal ubiquitination sites. Nat Struct Mol Biol. 2018;25(7):631\u201340.","journal-title":"Nat Struct Mol Biol"},{"issue":"1","key":"575_CR95","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1038\/s41467-017-01271-3","volume":"8","author":"RJ Lumpkin","year":"2017","unstructured":"Lumpkin RJ, et al. Site-specific identification and quantitation of endogenous SUMO modifications under native conditions. Nat Commun. 2017;8(1):1171.","journal-title":"Nat Commun"},{"issue":"3","key":"575_CR96","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1074\/mcp.O112.027094","volume":"12","author":"ND Udeshi","year":"2013","unstructured":"Udeshi ND, et al. Refined preparation and use of anti-diglycine remnant (K-epsilon-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments. Mol Cell Proteomics. 2013;12(3):825\u201331.","journal-title":"Mol Cell Proteomics"},{"issue":"4","key":"575_CR97","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004130","volume":"11","author":"J Palacios-Moreno","year":"2015","unstructured":"Palacios-Moreno J, et al. Neuroblastoma tyrosine kinase signaling networks involve FYN and LYN in endosomes and lipid rafts. PLoS Comput Biol. 2015;11(4):e1004130.","journal-title":"PLoS Comput Biol"},{"issue":"11","key":"575_CR98","doi-asserted-by":"publisher","first-page":"4581","DOI":"10.1021\/pr500418w","volume":"13","author":"H Johnson","year":"2014","unstructured":"Johnson H, White FM. Quantitative analysis of signaling networks across differentially embedded tumors highlights interpatient heterogeneity in human glioblastoma. J Proteome Res. 2014;13(11):4581\u201393.","journal-title":"J Proteome Res"},{"key":"575_CR99","unstructured":"H, L., et al., Post-Translational Modifications and Quality Control in the Rough ER, in Molecular Cell Biology. 2000, W. H. Freeman: New York."},{"issue":"22","key":"575_CR100","doi-asserted-by":"publisher","first-page":"RC107","DOI":"10.1523\/JNEUROSCI.20-22-j0004.2000","volume":"20","author":"TJ Ribar","year":"2000","unstructured":"Ribar TJ, et al. Cerebellar defects in Ca2+\/calmodulin kinase IV-deficient mice. J Neurosci. 2000;20(22):RC107.","journal-title":"J Neurosci"},{"issue":"5","key":"575_CR101","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1093\/brain\/aww064","volume":"139","author":"JD Schmahmann","year":"2016","unstructured":"Schmahmann JD. Cerebellum in Alzheimer\u2019s disease and frontotemporal dementia: not a silent bystander. Brain. 2016;139(5):1314\u20138.","journal-title":"Brain"},{"issue":"1","key":"575_CR102","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1093\/brain\/awx194","volume":"141","author":"HIL Jacobs","year":"2018","unstructured":"Jacobs HIL, et al. The cerebellum in Alzheimer's disease: evaluating its role in cognitive decline. Brain. 2018;141(1):37\u201347.","journal-title":"Brain"},{"key":"575_CR103","doi-asserted-by":"crossref","unstructured":"Hoxha E, et al. The Emerging Role of Altered Cerebellar Synaptic Processing in Alzheimer\u2019s Disease. Front Aging Neurosci. 2018;10(396):542\u201352.","DOI":"10.3389\/fnagi.2018.00396"},{"issue":"2","key":"575_CR104","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/0022-510X(89)90197-4","volume":"93","author":"H Braak","year":"1989","unstructured":"Braak H, et al. Alzheimer's disease: amyloid plaques in the cerebellum. J Neurol Sci. 1989;93(2):277\u201387.","journal-title":"J Neurol Sci"},{"issue":"6","key":"575_CR105","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1007\/BF00334682","volume":"85","author":"K. A. Jellinger","year":"1993","unstructured":"Jellinger KA. Distribution of amyloid plaques in the cerebellum in Alzheimer's disease. Acta Neuropathol. 1993;85(6):682.","journal-title":"Acta Neuropathologica"},{"issue":"4","key":"575_CR106","first-page":"188","volume":"8","author":"G Cole","year":"1989","unstructured":"Cole G, et al. Amyloid plaques in the cerebellum in Alzheimer's disease. Clin Neuropathol. 1989;8(4):188\u201391.","journal-title":"Clin Neuropathol"},{"issue":"3","key":"575_CR107","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1159\/000106625","volume":"8","author":"J Takamatsu","year":"1997","unstructured":"Takamatsu J, et al. Subpial amyloid plaques in the cerebellum in a case of Alzheimer's disease. Dement Geriatr Cogn Disord. 1997;8(3):157\u201362.","journal-title":"Dement Geriatr Cogn Disord"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-020-00575-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-020-00575-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-020-00575-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T02:52:38Z","timestamp":1666666358000},"score":1,"resource":{"primary":{"URL":"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-020-00575-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,27]]},"references-count":107,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["575"],"URL":"https:\/\/doi.org\/10.1186\/s12964-020-00575-0","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,27]]},"assertion":[{"value":"6 February 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The author MGS declares that he isthe\u00a0co-founder of, have an equity interest in, Alzo Biosciences Inc., a company that has licensed IP from the University of Manitoba and may potentially benefit from the research contained herein. The terms of this arrangement have been reviewed and approved by the University of Manitoba in accordance with its conflict of interest policies.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"80"}}