Activin signaling as an emerging target for therapeutic interventions. Export

@article{citeulike:4959979, abstract = {ABSTRACT: After the initial discovery of activins as important regulators of reproduction, novel and diverse roles have been unraveled for them. Activins are expressed in various tissues and have a broad range of activities including the regulation of gonadal function, hormonal homeostasis, growth and differentiation of musculoskeletal tissues, regulation of growth and metastasis of cancer cells, proliferation and differentiation of embryonic stem cells, and even higher brain functions. Activins signal through a combination of type I and II transmembrane serine/threonine kinase receptors. Activin receptors are shared by multiple transforming growth factor-beta (TGF-beta) ligands such as myostatin, growth and differentiation factor-11 and nodal. Thus, although the activity of each ligand is distinct, they are also redundant, both physiologically and pathologically in vivo. Activin receptors activated by ligands phosphorylate the receptor-regulated Smads for TGF-beta, Smad2 and 3. The Smad proteins then undergo multimerization with the co-mediator Smad4, and translocate into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. Signaling through receptors and Smads is controlled by multiple mechanisms including phosphorylation and other posttranslational modifications such as sumoylation, which affect potein localization, stability and transcriptional activity. Non-Smad signaling also plays an important role in activin signaling. Extracellularly, follistatin and related proteins bind to activins and related TGF-beta ligands, and control the signaling and availability of ligands.The functions of activins through activin receptors are pleiotrophic, cell type-specific and contextual, and they are involved in the etiology and pathogenesis of a variety of diseases. Accordingly, activin signaling may be a target for therapeutic interventions. In this review, we summarize the current knowledge on activin signaling and discuss the potential roles of this pathway as a molecular target of therapy for metabolic diseases, musculoskeletal disorders, cancers and neural damages.}, author = {Tsuchida, Kunihiro and Nakatani, Masashi and Hitachi, Keisuke and Uezumi, Akiyoshi and Sunada, Yoshihide and Ageta, Hiroshi and Inokuchi, Kaoru}, citeulike-article-id = {4959979}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1478-811X-7-15}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19538713}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19538713}, day = {18}, doi = {10.1186/1478-811X-7-15}, issn = {1478-811X}, journal = {Cell communication and signaling : CCS}, keywords = {activin}, month = {June}, pages = {15+}, posted-at = {2009-06-26 16:45:05}, priority = {2}, title = {Activin signaling as an emerging target for therapeutic interventions.}, url = {http://dx.doi.org/10.1186/1478-811X-7-15}, volume = {7}, year = {2009} }

TY - JOUR ID - citeulike:4959979 L3 - citeulike-article-id:4959979 N2 - ABSTRACT: After the initial discovery of activins as important regulators of reproduction, novel and diverse roles have been unraveled for them. Activins are expressed in various tissues and have a broad range of activities including the regulation of gonadal function, hormonal homeostasis, growth and differentiation of musculoskeletal tissues, regulation of growth and metastasis of cancer cells, proliferation and differentiation of embryonic stem cells, and even higher brain functions. Activins signal through a combination of type I and II transmembrane serine/threonine kinase receptors. Activin receptors are shared by multiple transforming growth factor-beta (TGF-beta) ligands such as myostatin, growth and differentiation factor-11 and nodal. Thus, although the activity of each ligand is distinct, they are also redundant, both physiologically and pathologically in vivo. Activin receptors activated by ligands phosphorylate the receptor-regulated Smads for TGF-beta, Smad2 and 3. The Smad proteins then undergo multimerization with the co-mediator Smad4, and translocate into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. Signaling through receptors and Smads is controlled by multiple mechanisms including phosphorylation and other posttranslational modifications such as sumoylation, which affect potein localization, stability and transcriptional activity. Non-Smad signaling also plays an important role in activin signaling. Extracellularly, follistatin and related proteins bind to activins and related TGF-beta ligands, and control the signaling and availability of ligands.The functions of activins through activin receptors are pleiotrophic, cell type-specific and contextual, and they are involved in the etiology and pathogenesis of a variety of diseases. Accordingly, activin signaling may be a target for therapeutic interventions. In this review, we summarize the current knowledge on activin signaling and discuss the potential roles of this pathway as a molecular target of therapy for metabolic diseases, musculoskeletal disorders, cancers and neural damages. JF - Cell communication and signaling : CCS SN - 1478-811X TI - Activin signaling as an emerging target for therapeutic interventions. VL - 7 SP - 15 KW - activin AU - Tsuchida, Kunihiro AU - Nakatani, Masashi AU - Hitachi, Keisuke AU - Uezumi, Akiyoshi AU - Sunada, Yoshihide AU - Ageta, Hiroshi AU - Inokuchi, Kaoru PY - 2009/06/18/ UR - http://dx.doi.org/10.1186/1478-811X-7-15 ER -