{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:03:21Z","timestamp":1789592601628,"version":"build-2803163510"},"reference-count":104,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Familial isolated pituitary adenoma (FIPA) is caused in about 20% of cases by loss-of-function germline mutations in the AIP gene. Patients harboring AIP mutations usually present with somatotropinomas resulting either in gigantism or young-onset acromegaly. AIP encodes for a co-chaperone protein endowed with tumor suppressor properties in somatotroph cells. Among other mechanisms proposed to explain this function, a regulatory effect over the 3\u2032,5\u2032-cyclic adenosine monophosphate (cAMP) signaling pathway seems to play a prominent role. In this setting, the well-known interaction between AIP and 2 different isoforms of phosphodiesterases (PDEs), PDE2A3 and PDE4A5, is of particular interest. While the interaction with over-expressed AIP does not seem to affect PDE2A3 function, the reported effect on PDE4A5 is, in contrast, reduced enzymatic activity. In this review, we explore the possible implications of these molecular interactions for the function of somatotroph cells. In particular, we discuss how both PDEs and AIP could act as negative regulators of the cAMP pathway in the pituitary, probably both by shared and independent mechanisms. Moreover, we describe how the evaluation of the AIP-PDE4A5 interaction has proven to be a useful tool for testing AIP mutations, complementing other in silico, in vitro, and in vivo analyses. Improved assessment of the pathogenicity of AIP mutations is indeed paramount to provide adequate guidance for genetic counseling and clinical screening in AIP mutation carriers, which can lead to prospective diagnosis of pituitary adenomas.<\/jats:p>","DOI":"10.1055\/s-0043-104700","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T22:31:28Z","timestamp":1492727488000},"page":"286-295","source":"Crossref","is-referenced-by-count":17,"title":["Role of Phosphodiesterases on the Function of Aryl Hydrocarbon Receptor-Interacting Protein (AIP) in the Pituitary Gland and on the Evaluation of AIP Gene Variants"],"prefix":"10.1055","volume":"49","author":[{"given":"Laura C.","family":"Hern\u00e1ndez-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Trivellin","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine A.","family":"Stratakis","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2017,4,20]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1210\/jc.2005-2671","article-title":"Clinical characterization of familial isolated pituitary adenomas","volume":"91","author":"A F Daly","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1126\/science.1126100","article-title":"Pituitary adenoma predisposition caused by germline mutations in the AIP gene","volume":"312","author":"O Vierimaa","year":"2006","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"E373","DOI":"10.1210\/jc.2009-2556","article-title":"Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study","volume":"95","author":"A F Daly","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1210\/er.2012-1013","article-title":"Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene","volume":"34","author":"A Beckers","year":"2013","journal-title":"Endocr Rev"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"E1242","DOI":"10.1210\/jc.2015-1869","article-title":"Landscape of familial isolated and young-onset pituitary adenomas: Prospective diagnosis in AIP mutation carriers","volume":"100","author":"L C Hern\u00e1ndez-Ram\u00edrez","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1056\/NEJMoa1408028","article-title":"Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation","volume":"371","author":"G Trivellin","year":"2014","journal-title":"N Engl J Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1530\/ERC-15-0038","article-title":"X-linked acrogigantism (X-LAG) syndrome: clinical profile and therapeutic responses","volume":"22","author":"A Beckers","year":"2015","journal-title":"Endocr Relat Cancer"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1530\/ERC-16-0082","article-title":"Somatic mosaicism underlies X-linked acrogigantism (XLAG) syndrome in sporadic male subjects","volume":"23","author":"A F Daly","year":"2016","journal-title":"Endocr Relat Cancer"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40478-016-0328-1","article-title":"Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study","volume":"4","author":"D Iacovazzo","year":"2016","journal-title":"Acta Neuropathol Commun"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1007\/s11102-016-0743-0","article-title":"Childhood acromegaly due to X-linked acrogigantism: long term follow-up","volume":"19","author":"R J Gordon","year":"2016","journal-title":"Pituitary"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"L17","DOI":"10.1530\/ERC-16-0558","article-title":"Paleogenetic study of ancient DNA suggestive of X-Linked acrogigantism","volume":"24","author":"A Beckers","year":"2017","journal-title":"Endocr Relat Cancer"},{"key":"ref12","first-page":"249","article-title":"Loss of heterozygosity on chromosome 11q13 in two families with acromegaly\/gigantism is independent of mutations of the multiple endocrine neoplasia type I gene","volume":"84","author":"M R Gadelha","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"ref13","first-page":"707","article-title":"Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12","volume":"85","author":"M R Gadelha","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"ref14","first-page":"165","article-title":"Isolated familial somatotropinomas: clinical and genetic considerations","volume":"114","author":"L A Frohman","year":"2003","journal-title":"Trans Am Clin Climatol Assoc"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"L11","DOI":"10.1530\/ERC-13-0218","article-title":"Familial pituitary apoplexy as the only presentation of a novel AIP mutation","volume":"20","author":"P Xekouki","year":"2013","journal-title":"Endocr Relat Cancer"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1530\/ERC-13-0043","article-title":"Aip regulates cAMP signalling and GH secretion in GH3 cells","volume":"20","author":"R Formosa","year":"2013","journal-title":"Endocr Relat Cancer"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1038\/onc.2014.50","article-title":"AIP inactivation leads to pituitary tumorigenesis through defective Galphai-cAMP signaling","volume":"34","author":"I Tuominen","year":"2015","journal-title":"Oncogene"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"8878","DOI":"10.1074\/jbc.272.14.8878","article-title":"A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"272","author":"Q Ma","year":"1997","journal-title":"J Biol Chem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"33580","DOI":"10.1074\/jbc.273.50.33580","article-title":"Characterization of the Ah receptor-associated protein, ARA9","volume":"273","author":"L A Carver","year":"1998","journal-title":"J Biol Chem"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e53339","DOI":"10.1371\/journal.pone.0053339","article-title":"Structure of the TPR domain of AIP: Lack of client protein interaction with the C-terminal alpha-7 helix of the TPR domain of AIP is sufficient for pituitary adenoma predisposition","volume":"7","author":"R M Morgan","year":"2012","journal-title":"PLoS One"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s12104-012-9359-0","article-title":"NMR assignments of the FKBP-type PPIase domain of the human aryl-hydrocarbon receptor-interacting protein (AIP)","volume":"6","author":"M Linnert","year":"2012","journal-title":"Biomol NMR Assign"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"D204","DOI":"10.1093\/nar\/gku989","article-title":"UniProt: a hub for protein information (http:\/\/www.uniprot.org\/)","volume":"43","author":"The Uniprot Consortium","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0003-9861(02)00444-7","article-title":"Characterization of the phosphorylation status of the hepatitis B virus X-associated protein 2","volume":"406","author":"A B Dull","year":"2002","journal-title":"Arch Biochem Biophys"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1379\/1466-1268(2000)005<0243:AHARLA>2.0.CO;2","article-title":"Aryl hydrocarbon (Ah) receptor levels are selectively modulated by hsp90-associated immunophilin homolog XAP2","volume":"5","author":"B K Meyer","year":"2000","journal-title":"Cell Stress Chaperones"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.1093\/nar\/24.23.4741","article-title":"XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation","volume":"24","author":"N Kuzhandaivelu","year":"1996","journal-title":"Nucleic Acids Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"11452","DOI":"10.1074\/jbc.272.17.11452","article-title":"Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo","volume":"272","author":"L A Carver","year":"1997","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1021\/bi301649m","article-title":"The FKBP-type domain of the human aryl hydrocarbon receptor-interacting protein reveals an unusual Hsp90 interaction","volume":"52","author":"M Linnert","year":"2013","journal-title":"Biochemistry"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"D662","DOI":"10.1093\/nar\/gku1010","article-title":"Ensembl 2015","volume":"43","author":"F Cunningham","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1210\/jc.2007-2611","article-title":"The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas","volume":"93","author":"C A Leontiou","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1677\/ERC-09-0094","article-title":"Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications","volume":"16","author":"M L Jaffrain-Rea","year":"2009","journal-title":"Endocr Relat Cancer"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1007\/s00018-006-6215-3","article-title":"Immunophilins: for the love of proteins","volume":"63","author":"S Barik","year":"2006","journal-title":"Cell Mol Life Sci"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/978-3-319-11731-7_2","article-title":"Functions of the Hsp90-binding FKBP immunophilins","volume":"78","author":"N C Guy","year":"2015","journal-title":"Subcell Biochem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.tibs.2003.10.007","article-title":"TPR proteins: the versatile helix","volume":"28","author":"L D D\u2019Andrea","year":"2003","journal-title":"Trends Biochem Sci"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.str.2012.01.006","article-title":"Structural and functional discussion of the tetra-trico-peptide repeat, a protein interaction module","volume":"20","author":"N Zeytuni","year":"2012","journal-title":"Structure"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"13802","DOI":"10.1016\/S0021-9258(18)68314-0","article-title":"Association of the Ah receptor with the 90-kDa heat shock protein","volume":"263","author":"G H Perdew","year":"1988","journal-title":"J Biol Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"27554","DOI":"10.1016\/S0021-9258(18)47020-2","article-title":"Subunit composition of the heteromeric cytosolic aryl hydrocarbon receptor complex","volume":"269","author":"H S Chen","year":"1994","journal-title":"J Biol Chem"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1379\/1466-1268(1996)001<0237:APOMCI>2.3.CO;2","article-title":"A pathway of multi-chaperone interactions common to diverse regulatory proteins: estrogen receptor, Fes tyrosine kinase, heat shock transcription factor Hsf1, and the aryl hydrocarbon receptor","volume":"1","author":"S C Nair","year":"1996","journal-title":"Cell Stress Chaperones"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1128\/MCB.18.2.978","article-title":"Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity","volume":"18","author":"B K Meyer","year":"1998","journal-title":"Mol Cell Biol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1128\/MCB.21.7.2594-2607.2001","article-title":"The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor","volume":"21","author":"A Kazlauskas","year":"2001","journal-title":"Mol Cell Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1021\/bi035827v","article-title":"Divergent roles of hepatitis B virus X-associated protein 2 (XAP2) in human versus mouse Ah receptor complexes","volume":"43","author":"P Ramadoss","year":"2004","journal-title":"Biochemistry"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1021\/tx00036a003","article-title":"Mechanistic aspects of dioxin action","volume":"6","author":"J P Whitlock Jr.","year":"1993","journal-title":"Chem Res Toxicol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"36407","DOI":"10.1074\/jbc.M004236200","article-title":"Binding of aryl hydrocarbon receptor (AhR) to AhR-interacting protein. The role of hsp90","volume":"275","author":"D R Bell","year":"2000","journal-title":"J Biol Chem"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1615\/CritRevEukarGeneExpr.v18.i3.20","article-title":"The aryl hydrocarbon receptor complex and the control of gene expression","volume":"18","author":"T V Beischlag","year":"2008","journal-title":"Crit Rev Eukaryot Gene Expr"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/toxsci\/kfr218","article-title":"Exactly the same but different: promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor","volume":"124","author":"M S Denison","year":"2011","journal-title":"Toxicol Sci"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1021\/tx7001965","article-title":"The search for endogenous activators of the aryl hydrocarbon receptor","volume":"21","author":"L P Nguyen","year":"2008","journal-title":"Chem Res Toxicol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"35599","DOI":"10.1074\/jbc.M110.132043","article-title":"The aryl hydrocarbon receptor-interacting protein (AIP) is required for dioxin-induced hepatotoxicity but not for the induction of the Cyp1a1 and Cyp1a2 genes","volume":"285","author":"M Nukaya","year":"2010","journal-title":"J Biol Chem"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature10491","article-title":"An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor","volume":"478","author":"C A Opitz","year":"2011","journal-title":"Nature"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1083\/jcb.200305051","article-title":"AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins","volume":"163","author":"M Yano","year":"2003","journal-title":"J Cell Biol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"24721","DOI":"10.1074\/jbc.M603175200","article-title":"Regulation of survivin stability by the aryl hydrocarbon receptor-interacting protein","volume":"281","author":"B H Kang","year":"2006","journal-title":"J Biol Chem"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"16758","DOI":"10.1074\/jbc.M110.210120","article-title":"Developmental control of apoptosis by the immunophilin aryl hydrocarbon receptor-interacting protein (AIP) involves mitochondrial import of the survivin protein","volume":"286","author":"B H Kang","year":"2011","journal-title":"J Biol Chem"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.pharmthera.2012.08.014","article-title":"Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential","volume":"136","author":"T Liu","year":"2012","journal-title":"Pharmacol Ther"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.cell.2012.10.051","article-title":"CDK-dependent Hsp70 phosphorylation controls G1 cyclin abundance and cell-cycle progression","volume":"151","author":"A W Truman","year":"2012","journal-title":"Cell"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1038\/sj.onc.1203501","article-title":"Epstein-Barr virus encoded nuclear protein EBNA-3 binds XAP-2, a protein associated with Hepatitis B virus X antigen","volume":"19","author":"E Kashuba","year":"2000","journal-title":"Oncogene"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"D535","DOI":"10.1093\/nar\/gkj109","article-title":"BioGRID: a general repository for interaction datasets","volume":"34","author":"C Stark","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1530\/JOE-11-0054","article-title":"AIP and its interacting partners","volume":"210","author":"G Trivellin","year":"2011","journal-title":"J Endocrinol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1152\/physrev.1995.75.4.725","article-title":"Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms","volume":"75","author":"J A Beavo","year":"1995","journal-title":"Physiol Rev"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.pharmthera.2005.07.003","article-title":"Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents","volume":"109","author":"C Lugnier","year":"2006","journal-title":"Pharmacol Ther"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1146\/annurev.biochem.76.060305.150444","article-title":"Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling","volume":"76","author":"M Conti","year":"2007","journal-title":"Annu Rev Biochem"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1152\/physrev.00030.2010","article-title":"Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions","volume":"91","author":"S H Francis","year":"2011","journal-title":"Physiol Rev"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"391","DOI":"10.2174\/156802607779941242","article-title":"Crystal structures of phosphodiesterases and implications on substrate specificity and inhibitor selectivity","volume":"7","author":"H Ke","year":"2007","journal-title":"Curr Top Med Chem"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1126\/science.288.5472.1822","article-title":"Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity","volume":"288","author":"R X Xu","year":"2000","journal-title":"Science"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1210\/er.2013-1053","article-title":"Clinical and molecular genetics of the phosphodiesterases (PDEs)","volume":"35","author":"M F Azevedo","year":"2014","journal-title":"Endocr Rev"},{"key":"ref67","first-page":"6558","article-title":"A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs","volume":"13","author":"G Bolger","year":"1993","journal-title":"Mol Cell Biol"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.2174\/138161210790963760","article-title":"Cyclic nucleotide phosphodiesterases (PDE) and peptide motifs","volume":"16","author":"T Keravis","year":"2010","journal-title":"Curr Pharm Des"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1042\/bj3280539","article-title":"Characterization of five different proteins produced by alternatively spliced mRNAs from the human cAMP-specific phosphodiesterase PDE4D gene","volume":"328","author":"G B Bolger","year":"1997","journal-title":"Biochem J"},{"key":"ref70","volume-title":"Cyclic nucleotide phosphodiesterases in health and disease","author":"G B Bolger","year":"2007"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4103\/2279-042X.167043","article-title":"A short review on structure and role of cyclic-3',5'-adenosine monophosphate-specific phosphodiesterase 4 as a treatment tool","volume":"4","author":"N Eskandari","year":"2015","journal-title":"J Res Pharm Pract"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0014-5793(94)00788-8","article-title":"Expression and regulation of human and rat phosphodiesterase type IV isogenes","volume":"350","author":"P Engels","year":"1994","journal-title":"FEBS Lett"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1530\/ERC-15-0205","article-title":"cAMP-specific PDE4 phosphodiesterases and AIP in the pathogenesis of pituitary tumors","volume":"23","author":"G B Bolger","year":"2016","journal-title":"Endocr Relat Cancer"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"28063","DOI":"10.1074\/jbc.M906144199","article-title":"The cAMP-specific phosphodiesterase PDE4A5 is cleaved downstream of its SH3 interaction domain by caspase-3. Consequences for altered intracellular distribution","volume":"275","author":"E Huston","year":"2000","journal-title":"J Biol Chem"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0898-6568(01)00264-9","article-title":"In addition to the SH3 binding region, multiple regions within the N-terminal noncatalytic portion of the cAMP-specific phosphodiesterase, PDE4A5, contribute to its intracellular targeting","volume":"14","author":"M B Beard","year":"2002","journal-title":"Cell Signal"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"33351","DOI":"10.1074\/jbc.M303269200","article-title":"Attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by interaction with the immunophilin XAP2","volume":"278","author":"G B Bolger","year":"2003","journal-title":"J Biol Chem"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1095\/biolreprod.105.043588","article-title":"AKAP3 selectively binds PDE4A isoforms in bovine spermatozoa","volume":"74","author":"M Bajpai","year":"2006","journal-title":"Biol Reprod"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"13260","DOI":"10.1073\/pnas.192374899","article-title":"The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding","volume":"99","author":"S E Martinez","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1124\/pr.58.3.5","article-title":"Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use","volume":"58","author":"A T Bender","year":"2006","journal-title":"Pharmacol Rev"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0378-1119(97)00046-2","article-title":"Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3\u2032,5\u2032-cyclic nucleotide phosphodiesterase","volume":"191","author":"G J Rosman","year":"1997","journal-title":"Gene"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1177\/002215549904700707","article-title":"Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A in human venous and capillary endothelial cells","volume":"47","author":"K Sadhu","year":"1999","journal-title":"J Histochem Cytochem"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1369\/jhc.2009.953471","article-title":"Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species","volume":"57","author":"D T Stephenson","year":"2009","journal-title":"J Histochem Cytochem"},{"key":"ref83","first-page":"P245","article-title":"Evaluation of the interaction of phosphodiesterases 2A and 4A5 with the aryl hydrocarbon receptor interacting protein in pituitary cells","volume":"Endocr Abstr 2011","author":"C Lennox","year":"2011","journal-title":"Soc Endocrinol BES"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"13656","DOI":"10.1074\/jbc.M610942200","article-title":"Phosphodiesterase 2A forms a complex with the co-chaperone XAP2 and regulates nuclear translocation of the aryl hydrocarbon receptor","volume":"282","author":"S K de Oliveira","year":"2007","journal-title":"J Biol Chem"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.bcp.2008.08.027","article-title":"Phosphodiesterases link the aryl hydrocarbon receptor complex to cyclic nucleotide signaling","volume":"77","author":"S K de Oliveira","year":"2009","journal-title":"Biochem Pharmacol"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1210\/er.2000-0026","article-title":"Insights into G protein structure, function, and regulation","volume":"24","author":"T M Cabrera-Vera","year":"2003","journal-title":"Endocr Rev"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mce.2010.04.027","article-title":"PRKAR1A and the evolution of pituitary tumors","volume":"326","author":"L S Kirschner","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.tem.2012.11.007","article-title":"Novel pathway for somatostatin analogs in patients with acromegaly","volume":"24","author":"M R Gadelha","year":"2013","journal-title":"Trends Endocrinol Metab"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"E1411","DOI":"10.1210\/jc.2012-1111","article-title":"Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway","volume":"97","author":"H S Chahal","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"L25","DOI":"10.1530\/ERC-12-0020","article-title":"AIP expression in sporadic somatotropinomas is a predictor of the response to octreotide LAR therapy independent of SSTR2 expression","volume":"19","author":"L Kasuki","year":"2012","journal-title":"Endocr Relat Cancer"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1159\/000322787","article-title":"Low aryl hydrocarbon receptor-interacting protein expression is a better marker of invasiveness in somatotropinomas than Ki-67 and p53","volume":"94","author":"P L Kasuki Jomori de","year":"2011","journal-title":"Neuroendocrinology"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1530\/ERC-12-0322","article-title":"Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations","volume":"20","author":"M L Jaffrain-Rea","year":"2013","journal-title":"Endocr Relat Cancer"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1158\/0008-5472.CAN-05-1189","article-title":"Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumor cells by altering phosphatidylinositol 3-kinase signaling and inducing Zac1 expression","volume":"66","author":"M Theodoropoulou","year":"2006","journal-title":"Cancer Res"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.pharmthera.2007.06.010","article-title":"An update on somatostatin receptor signaling in native systems and new insights on their pathophysiology","volume":"116","author":"D Cervia","year":"2007","journal-title":"Pharmacol Ther"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1530\/eje.0.1430279","article-title":"Role of phosphodiesterase and protein kinase G on nitric oxide-induced inhibition of prolactin release from the rat anterior pituitary","volume":"143","author":"M O Velardez","year":"2000","journal-title":"Eur J Endocrinol"},{"key":"ref96","first-page":"1624","article-title":"Constitutively active Gs alpha is associated with an increased phosphodiesterase activity in human growth hormone-secreting adenomas","volume":"83","author":"A Lania","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"ref97","first-page":"3795","article-title":"Relevant cAMP-specific phosphodiesterase isoforms in human pituitary: effect of Gs(alpha) mutations","volume":"86","author":"L Persani","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1530\/EJE-09-0677","article-title":"Analysis of genetic variants of phosphodiesterase 11A in acromegalic patients","volume":"161","author":"E Peverelli","year":"2009","journal-title":"Eur J Endocrinol"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"R67","DOI":"10.1530\/JME-13-0172","article-title":"cAMP in the pituitary: an old messenger for multiple signals","volume":"52","author":"E Peverelli","year":"2014","journal-title":"J Mol Endocrinol"},{"key":"ref100","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1042\/BJ20101184","article-title":"Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase A phosphorylation","volume":"435","author":"K F MacKenzie","year":"2011","journal-title":"Biochem J"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"13897","DOI":"10.1073\/pnas.0404197101","article-title":"Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase","volume":"101","author":"V Ramamurthy","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1210\/jc.2013-2868","article-title":"Clinical experience in the screening and management of a large kindred with familial isolated pituitary adenoma due to an aryl hydrocarbon receptor interacting protein (AIP) mutation","volume":"99","author":"F Williams","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1210\/jc.2016-1307","article-title":"Rapid proteasomal degradation of mutant proteins is the primary mechanism leading to tumorigenesis in patients with missense AIP mutations","volume":"101","author":"L C Hern\u00e1ndez-Ram\u00edrez","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1749-6632.2002.tb04327.x","article-title":"Role of the PKA-regulated transcription factor CREB in development and tumorigenesis of endocrine tissues","volume":"968","author":"D Rosenberg","year":"2002","journal-title":"Ann NY Acad Sci"},{"key":"ref107","doi-asserted-by":"crossref","first-page":"E370","DOI":"10.1152\/ajpendo.00130.2011","article-title":"Role of nonselective cation channels in spontaneous and protein kinase A-stimulated calcium signaling in pituitary cells","volume":"301","author":"M Tomic","year":"2011","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"9828","DOI":"10.1073\/pnas.91.21.9828","article-title":"Mechanism of GTP hydrolysis by G-protein alpha subunits","volume":"91","author":"C Kleuss","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00294-002-0308-9","article-title":"Molecular mechanisms controlling the localisation of protein kinase A","volume":"41","author":"G Griffioen","year":"2002","journal-title":"Curr Genet"},{"key":"ref110","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.tem.2009.12.003","article-title":"Pituitary somatostatin receptor signaling","volume":"21","author":"A Ben-Shlomo","year":"2010","journal-title":"Trends Endocrinol Metab"}],"container-title":["Hormone and Metabolic 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