{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T14:19:49Z","timestamp":1780928389775,"version":"3.54.1"},"reference-count":51,"publisher":"Pensoft Publishers","issue":"3","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FM"],"abstract":"<jats:p>Recent research suggests that isoforms of myosin phosphatase target subunit 1 (MYPT1) may influence blood pressure regulation by altering smooth muscle responsiveness and, as a result, the function of vascularized tissues. Cloning and sequencing from diverse tissues and species revealed the existence of MYPT1 isoforms produced through alternative splicing, indicating their potential role in the regulation of blood pressure. Moreover, alterations in MYPT1 expression are linked to several diseases, including inflammatory bowel disease, gastric cancer, intestinal cancer, colon cancer, ovarian cancer, hypertension, and liver cirrhosis. These studies, although limited, suggest a novel role for the protein as an important diagnostic marker and a potential target for gene therapies. This review analyzes recent data about the role of MYPT1 in the regulation of vascular tone in both health and disease.<\/jats:p>","DOI":"10.3897\/folmed.68.e166432","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:26:41Z","timestamp":1780925201000},"source":"Crossref","is-referenced-by-count":0,"title":["The emerging function of MYPT1 as a biomarker and therapeutic target"],"prefix":"10.3897","volume":"68","author":[{"given":"Victor","family":"Velyanov","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, Medical University, Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"Lazarov","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Medical University, Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubomir","family":"Lubomirov","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Pathophysiology, Faculty of Health \u2013 School of Medicine, Biomedical Center for Education and Research (ZBAF), Witten\/Herdecke University, Witten, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6235-3384","authenticated-orcid":true,"given":"Kameliya","family":"Bratoeva","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Medical University, Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2258","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"166432_B1","doi-asserted-by":"crossref","unstructured":"Bayliss WM. On the local reactions of the arterial wall to changes of internal pressure. J Physiol 1902;28(3):220\u201331.","DOI":"10.1113\/jphysiol.1902.sp000911"},{"key":"166432_B2","doi-asserted-by":"crossref","unstructured":"Davis MJ, Hill MA. Signaling mechanisms underlying the vascular myogenic response. Physiol Rev 1999;79(2):387\u2013423.","DOI":"10.1152\/physrev.1999.79.2.387"},{"key":"166432_B3","doi-asserted-by":"crossref","unstructured":"Bolz SS, Pieperhoff S, De Wit C, et al. Intact endothelial and smooth muscle function in small resistance arteries after 48 h in vessel culture. Am J Physiol Heart Circ Physiol 2000;279(3):H1434\u20139.","DOI":"10.1152\/ajpheart.2000.279.3.H1434"},{"key":"166432_B4","doi-asserted-by":"crossref","unstructured":"El-Yazbi AF, Johnson RP, Walsh EJ, et al. Pressure-dependent contribution of Rho kinase-mediated calcium sensitization in serotonin-evoked vasoconstriction of rat cerebral arteries. J Physiol 2010;588(Pt 10):1747\u201362.","DOI":"10.1113\/jphysiol.2010.187146"},{"key":"166432_B5","doi-asserted-by":"crossref","unstructured":"Johnson RP, El-Yazbi AF, Takeya K, et al. Ca2+ sensitization via phosphorylation of myosin phosphatase targeting subunit at threonine-855 by Rho kinase contributes to the arterial myogenic response. J Physiol 2009;587(Pt 11):2537\u201353.","DOI":"10.1113\/jphysiol.2008.168252"},{"key":"166432_B6","doi-asserted-by":"crossref","unstructured":"Schubert R, Lidington D, Bolz SS. The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction. Cardiovasc Res 2008;77(1):8\u201318.","DOI":"10.1016\/j.cardiores.2007.07.018"},{"key":"166432_B7","doi-asserted-by":"crossref","unstructured":"Faraci FM, Heistad DD. Regulation of large cerebral arteries and cerebral microvascular pressure. Circ Res 1990;66(1):8\u201317.","DOI":"10.1161\/01.RES.66.1.8"},{"key":"166432_B8","doi-asserted-by":"crossref","unstructured":"Biwer LA, Lu Q, Ibarrola J, et al. Smooth muscle mineralocorticoid receptor promotes hypertension after preeclampsia. Circ Res 2023;132(6):674\u201389.","DOI":"10.1161\/CIRCRESAHA.122.321228"},{"key":"166432_B9","doi-asserted-by":"crossref","unstructured":"Carlstrom M, Wilcox CS, Arendshorst WJ. Renal autoregulation in health and disease. Physiol Rev 2015;95(2):405\u2013511.","DOI":"10.1152\/physrev.00042.2012"},{"key":"166432_B10","doi-asserted-by":"crossref","unstructured":"Jensen LJ. Functional, structural and proteomic effects of ageing in resistance arteries. Int J Mol Sci 2024;25(5):2601.","DOI":"10.3390\/ijms25052601"},{"key":"166432_B11","doi-asserted-by":"crossref","unstructured":"Ulke-Lemee A, MacDonald JA. Opportunities to target specific contractile abnormalities with smooth muscle protein kinase inhibitors. Pharmaceuticals (Basel) 2010;3(6):1739\u201360.","DOI":"10.3390\/ph3061739"},{"key":"166432_B12","doi-asserted-by":"crossref","unstructured":"Cole WC, Welsh DG. Role of myosin light chain kinase and myosin light chain phosphatase in the resistance arterial myogenic response to intravascular pressure. Arch Biochem Biophys 2011;510(2): 160\u201373.","DOI":"10.1016\/j.abb.2011.02.024"},{"key":"166432_B13","doi-asserted-by":"crossref","unstructured":"Somlyo AP, Somlyo AV. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 2003;83(4):1325\u201358.","DOI":"10.1152\/physrev.00023.2003"},{"key":"166432_B14","doi-asserted-by":"crossref","unstructured":"Tansey MG, Luby-Phelps K, Kamm KE, et al. Ca2+-dependent phosphorylation of myosin light chain kinase decreases the Ca2+ sensitivity of light chain phosphorylation within smooth muscle cells. J Biol Chem 1994;269(13):9912\u201320.","DOI":"10.1016\/S0021-9258(17)36969-7"},{"key":"166432_B15","doi-asserted-by":"crossref","unstructured":"Lubomirov LT, Papadopoulos S, Filipova D, et al. The involvement of phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and MYPT1 isoform expression in NO\/cGMP mediated differential vasoregulation of cerebral arteries compared to systemic arteries. Acta Physiol (Oxf) 2018;224(1):e13079.","DOI":"10.1111\/apha.13079"},{"key":"166432_B16","doi-asserted-by":"crossref","unstructured":"Pfitzer G, Lubomirov LT, Reimann K, et al. Regulation of the crossbridge cycle in vascular smooth muscle by cAMP signalling. J Muscle Res Cell Motil 2006;27(5-7):445\u201354.","DOI":"10.1007\/s10974-006-9097-y"},{"key":"166432_B17","doi-asserted-by":"crossref","unstructured":"Hirano K. Current topics in the regulatory mechanism underlying the Ca2+ sensitization of the contractile apparatus in vascular smooth muscle. J Pharmacol Sci 2007;104(2):109\u201315.","DOI":"10.1254\/jphs.CP0070027"},{"key":"166432_B18","doi-asserted-by":"crossref","unstructured":"Grassie ME, Moffat LD, Walsh MP, et al. The myosin phosphatase targeting protein (MYPT) family: a regulated mechanism for achieving substrate specificity of the catalytic subunit of protein phosphatase type 1 delta. Arch Biochem Biophys 2011;510(2):147\u201359.","DOI":"10.1016\/j.abb.2011.01.018"},{"key":"166432_B19","doi-asserted-by":"crossref","unstructured":"Feng J, Ito M, Ichikawa K, et al. Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase. J Biol Chem 1999;274(52):37385\u201390.","DOI":"10.1074\/jbc.274.52.37385"},{"key":"166432_B20","doi-asserted-by":"crossref","unstructured":"Chen CP, Chen X, Qiao YN, et al. In vivo roles for myosin phosphatase targeting subunit-1 phosphorylation sites T694 and T852 in bladder smooth muscle contraction. J Physiol 2015;593(3):681\u2013700.","DOI":"10.1113\/jphysiol.2014.283853"},{"key":"166432_B21","doi-asserted-by":"crossref","unstructured":"Lubomirov LT, Papadopoulos S, Putz S, et al. Aging-related alterations in eNOS and nNOS responsiveness and smooth muscle reactivity of murine basilar arteries are modulated by apocynin and phosphorylation of myosin phosphatase targeting subunit-1. J Cereb Blood Flow Metab 2017;37(3):1014\u201329.","DOI":"10.1177\/0271678X16649402"},{"key":"166432_B22","doi-asserted-by":"crossref","unstructured":"Khromov A, Choudhury N, Stevenson AS, et al. Phosphorylation-dependent autoinhibition of myosin light chain phosphatase accounts for Ca2+ sensitization force of smooth muscle contraction. J Biol Chem 2009;284(32):21569\u201379.","DOI":"10.1074\/jbc.M109.019729"},{"key":"166432_B23","doi-asserted-by":"crossref","unstructured":"Lubomirov LT, Weber G, Schroeter M, et al. Alanine mutation of the targeting subunit of the myosin phosphatase, MYPT1 at threonine 696 reduces cGMP responsiveness of mouse femoral arteries. Eur J Pharmacol 2025;986:177133.","DOI":"10.1016\/j.ejphar.2024.177133"},{"key":"166432_B24","doi-asserted-by":"crossref","unstructured":"Wooldridge AA, MacDonald JA, Erdodi F, et al. Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. J Biol Chem 2004;279(33):34496\u2013504.","DOI":"10.1074\/jbc.M405957200"},{"key":"166432_B25","doi-asserted-by":"crossref","unstructured":"Yamashiro S, Yamakita Y, Totsukawa G, et al. Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing polo-like kinase 1. Dev Cell 2008;14(5):787\u201397.","DOI":"10.1016\/j.devcel.2008.02.013"},{"key":"166432_B26","doi-asserted-by":"crossref","unstructured":"Khatri JJ, Joyce KM, Brozovich FV, et al. Role of myosin phosphatase isoforms in cGMP-mediated smooth muscle relaxation. J Biol Chem 2001;276(40):37250\u20137.","DOI":"10.1074\/jbc.M105275200"},{"key":"166432_B27","doi-asserted-by":"crossref","unstructured":"Payne MC, Zhang HY, Shirasawa Y, et al. Dynamic changes in expression of myosin phosphatase in a model of portal hypertension. Am J Physiol Heart Circ Physiol 2004;286(5):H1801\u201310.","DOI":"10.1152\/ajpheart.00696.2003"},{"key":"166432_B28","doi-asserted-by":"crossref","unstructured":"Payne MC, Zhang HY, Prosdocimo T, et al. Myosin phosphatase isoform switching in vascular smooth muscle development. J Mol Cell Cardiol 2006;40(2):274\u201382.","DOI":"10.1016\/j.yjmcc.2005.07.009"},{"key":"166432_B29","doi-asserted-by":"crossref","unstructured":"Reho JJ, Kenchegowda D, Asico LD, et al. A splice variant of the myosin phosphatase regulatory subunit tunes arterial reactivity and suppresses response to salt loading. Am J Physiol Heart Circ Physiol 2016;310(11):H1715\u201324.","DOI":"10.1152\/ajpheart.00869.2015"},{"key":"166432_B30","doi-asserted-by":"crossref","unstructured":"Dirksen WP, Vladic F, Fisher SA. A myosin phosphatase targeting subunit isoform transition defines a smooth muscle developmental phenotypic switch. Am J Physiol Cell Physiol 2000;278(3):C589\u2013600.","DOI":"10.1152\/ajpcell.2000.278.3.C589"},{"key":"166432_B31","doi-asserted-by":"crossref","unstructured":"Fisher SA, Ikebe M, Brozovich F. Endothelin-1 alters the contractile phenotype of cultured embryonic smooth muscle cells. Circ Res 1997;80(6):885\u201393.","DOI":"10.1161\/01.RES.80.6.885"},{"key":"166432_B32","doi-asserted-by":"crossref","unstructured":"Dippold RP, Fisher SA. Myosin phosphatase isoforms as determinants of smooth muscle contractile function and calcium sensitivity of force production. Microcirculation 2014;21(3):239\u201348.","DOI":"10.1111\/micc.12097"},{"key":"166432_B33","doi-asserted-by":"crossref","unstructured":"Karim SM, Rhee AY, Given AM, et al. Vascular reactivity in heart failure: role of myosin light chain phosphatase. Circ Res 2004;95(6): 612\u20138.","DOI":"10.1161\/01.RES.0000142736.39359.58"},{"key":"166432_B34","doi-asserted-by":"crossref","unstructured":"Lubomirov LT, Jansch MH, Papadopoulos S, et al. Senescent murine femoral arteries undergo vascular remodelling associated with accelerated stress-induced contractility and reactivity to nitric oxide. Basic Clin Pharmacol Toxicol 2022;130(1):70\u201383.","DOI":"10.1111\/bcpt.13675"},{"key":"166432_B35","doi-asserted-by":"crossref","unstructured":"Cui Y, Yang L, Liu X, et al. Decrease of MYPT1 is critical for impairment of NO-mediated vasodilation in mesenteric artery of the older spontaneously hypertensive rats. J Gerontol A Biol Sci Med Sci 2022;77(3):424\u201332.","DOI":"10.1093\/gerona\/glab290"},{"key":"166432_B36","doi-asserted-by":"crossref","unstructured":"Ohama T, Hori M, Sato K, et al. Chronic treatment with interleukin-1beta attenuates contractions by decreasing the activities of CPI-17 and MYPT-1 in intestinal smooth muscle. J Biol Chem 2003;278(49):48794\u2013804.","DOI":"10.1074\/jbc.M310166200"},{"key":"166432_B37","doi-asserted-by":"crossref","unstructured":"Wang Y, Jiang ZH, Zhou YW, et al. Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice. Hepatol Commun 2024;8(7):e0473.","DOI":"10.1097\/HC9.0000000000000473"},{"key":"166432_B38","doi-asserted-by":"crossref","unstructured":"Belik J, Kerc E, Pato MD. Rat pulmonary arterial smooth muscle myosin light chain kinase and phosphatase activities decrease with age. Am J Physiol Lung Cell Mol Physiol 2006;290(3):L509\u201316.","DOI":"10.1152\/ajplung.00145.2005"},{"key":"166432_B39","doi-asserted-by":"crossref","unstructured":"Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol 2014;20(1):91\u20139.","DOI":"10.3748\/wjg.v20.i1.91"},{"key":"166432_B40","unstructured":"Kessmann J. Hirschsprung\u2019s disease: diagnosis and management. Am Fam Physician 2006;74(8):1319\u201322."},{"key":"166432_B41","doi-asserted-by":"crossref","unstructured":"Heuckeroth RO. Hirschsprung disease - integrating basic science and clinical medicine to improve outcomes. Nat Rev Gastroenterol Hepatol 2018;15(3):152\u201367.","DOI":"10.1038\/nrgastro.2017.149"},{"key":"166432_B42","doi-asserted-by":"crossref","unstructured":"Zhao W, Wang P, He W, et al. MYPT1 down-regulation by lipopolysaccharide-SIAH1\/2 E3 ligase-ubiquitin-proteasomal degradation contributes to colonic obstruction of Hirschsprung disease. Cell Mol Gastroenterol Hepatol 2020;9(2):345\u20137.","DOI":"10.1016\/j.jcmgh.2019.11.003"},{"key":"166432_B43","doi-asserted-by":"crossref","unstructured":"Li W, Sasse KC, Bayguinov Y, et al. Contractile protein expression and phosphorylation and contractility of gastric smooth muscles from obese patients and patients with obesity and diabetes. J Diabetes Res 2018;2018:8743874.","DOI":"10.1155\/2018\/8743874"},{"key":"166432_B44","doi-asserted-by":"crossref","unstructured":"Lubomirov LT, Gagov H, Schroeter MM, et al. Augmented contractility of murine femoral arteries in a streptozotocin diabetes model is related to increased phosphorylation of MYPT1. Physiol Rep 2019;7(3):e13975.","DOI":"10.14814\/phy2.13975"},{"key":"166432_B45","doi-asserted-by":"crossref","unstructured":"Joo EE, Yamada KM. MYPT1 regulates contractility and microtubule acetylation to modulate integrin adhesions and matrix assembly. Nat Commun 2014;5:3510.","DOI":"10.1038\/ncomms4510"},{"key":"166432_B46","doi-asserted-by":"crossref","unstructured":"Wang F, Sun Y. Overexpression of myosin phosphatase target subunit 1 (MYPT1) inhibits tumor progression and metastasis of gastric cancer. Med Sci Monit 2018;24:2508\u201317.","DOI":"10.12659\/MSM.906852"},{"key":"166432_B47","doi-asserted-by":"crossref","unstructured":"Munoz-Galvan S, Felipe-Abrio B, Verdugo-Sivianes EM, et al. Downregulation of MYPT1 increases tumor resistance in ovarian cancer by targeting the Hippo pathway and increasing the stemness. Mol Cancer 2020;19(1):7.","DOI":"10.1186\/s12943-020-1130-z"},{"key":"166432_B48","doi-asserted-by":"crossref","unstructured":"Zhang C, Xu C, Gao X, et al. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics 2022;12(5):2115\u201332.","DOI":"10.7150\/thno.69424"},{"key":"166432_B49","doi-asserted-by":"crossref","unstructured":"Wang Y, Wang L, Guo J, et al. MYPT1, regulated by miR-19b-3p inhibits the progression of non-small cell lung cancer via inhibiting the activation of wnt\/beta-catenin signaling. Life Sci 2021;278:119573.","DOI":"10.1016\/j.lfs.2021.119573"},{"key":"166432_B50","doi-asserted-by":"crossref","unstructured":"Ma H, He Q, Dou D, et al. Increased degradation of MYPT1 contributes to the development of tolerance to nitric oxide in porcine pulmonary artery. Am J Physiol Lung Cell Mol Physiol 2010;299(1): L117\u201323.","DOI":"10.1152\/ajplung.00340.2009"},{"key":"166432_B51","doi-asserted-by":"crossref","unstructured":"Xie Q, Liu R, Zou Zh, et al. MYPT1 inhibits the metastasis of renal clear cell carcinoma via the MAPK8\/N-cadherin pathway. FEBS Open Bio 2022;12(11):2083\u201395.","DOI":"10.1002\/2211-5463.13487"}],"container-title":["Folia Medica"],"original-title":[],"link":[{"URL":"https:\/\/foliamedica.bg\/article\/166432\/download\/pdf\/","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/foliamedica.bg\/article\/166432\/download\/xml\/","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/foliamedica.bg\/article_preview.php?id=166432&skip_redirect=1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:27:05Z","timestamp":1780925225000},"score":1,"resource":{"primary":{"URL":"https:\/\/foliamedica.bg\/article\/166432\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":51,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,6,8]]}},"URL":"https:\/\/doi.org\/10.3897\/folmed.68.e166432","relation":{},"ISSN":["1314-2143","0204-8043"],"issn-type":[{"value":"1314-2143","type":"electronic"},{"value":"0204-8043","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6,8]]},"article-number":"e166432"}}