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  • 1
    Publication Date: 1999-08-07
    Description: The actin cytoskeleton undergoes extensive remodeling during cell morphogenesis and motility. The small guanosine triphosphatase Rho regulates such remodeling, but the underlying mechanisms of this regulation remain unclear. Cofilin exhibits actin-depolymerizing activity that is inhibited as a result of its phosphorylation by LIM-kinase. Cofilin was phosphorylated in N1E-115 neuroblastoma cells during lysophosphatidic acid-induced, Rho-mediated neurite retraction. This phosphorylation was sensitive to Y-27632, a specific inhibitor of the Rho-associated kinase ROCK. ROCK, which is a downstream effector of Rho, did not phosphorylate cofilin directly but phosphorylated LIM-kinase, which in turn was activated to phosphorylate cofilin. Overexpression of LIM-kinase in HeLa cells induced the formation of actin stress fibers in a Y-27632-sensitive manner. These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maekawa, M -- Ishizaki, T -- Boku, S -- Watanabe, N -- Fujita, A -- Iwamatsu, A -- Obinata, T -- Ohashi, K -- Mizuno, K -- Narumiya, S -- New York, N.Y. -- Science. 1999 Aug 6;285(5429):895-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8315, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10436159" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*metabolism ; Actin Depolymerizing Factors ; Actins/metabolism ; Amides/pharmacology ; Animals ; COS Cells ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; GTP Phosphohydrolases/*metabolism ; GTP-Binding Proteins/*metabolism ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins ; Lim Kinases ; Lysophospholipids/pharmacology ; Membrane Proteins/*metabolism ; Microfilament Proteins/metabolism ; Phosphorylation ; Protein Kinases/*metabolism ; Protein-Serine-Threonine Kinases/*metabolism ; Pyridines/pharmacology ; *Signal Transduction ; Tumor Cells, Cultured ; rho-Associated Kinases ; rhoB GTP-Binding Protein
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2010-06-19
    Description: Adipose tissue secretes proteins referred to as adipokines, many of which promote inflammation and disrupt glucose homeostasis. Here we show that secreted frizzled-related protein 5 (Sfrp5), a protein previously linked to the Wnt signaling pathway, is an anti-inflammatory adipokine whose expression is perturbed in models of obesity and type 2 diabetes. Sfrp5-deficient mice fed a high-calorie diet developed severe glucose intolerance and hepatic steatosis, and their adipose tissue showed an accumulation of activated macrophages that was associated with activation of the c-Jun N-terminal kinase signaling pathway. Adenovirus-mediated delivery of Sfrp5 to mouse models of obesity ameliorated glucose intolerance and hepatic steatosis. Thus, in the setting of obesity, Sfrp5 secretion by adipocytes exerts salutary effects on metabolic dysfunction by controlling inflammatory cells within adipose tissue.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132938/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ouchi, Noriyuki -- Higuchi, Akiko -- Ohashi, Koji -- Oshima, Yuichi -- Gokce, Noyan -- Shibata, Rei -- Akasaki, Yuichi -- Shimono, Akihiko -- Walsh, Kenneth -- AG15052/AG/NIA NIH HHS/ -- AG34972/AG/NIA NIH HHS/ -- HL81587/HL/NHLBI NIH HHS/ -- HL86785/HL/NHLBI NIH HHS/ -- P01 HL081587/HL/NHLBI NIH HHS/ -- P01 HL081587-05/HL/NHLBI NIH HHS/ -- R01 AG015052/AG/NIA NIH HHS/ -- R01 AG015052-06/AG/NIA NIH HHS/ -- R01 AG034972/AG/NIA NIH HHS/ -- R01 AG034972-03/AG/NIA NIH HHS/ -- R01 HL086785/HL/NHLBI NIH HHS/ -- R01 HL086785-19/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):454-7. doi: 10.1126/science.1188280. Epub 2010 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Cardiology and Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA. nouchi@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20558665" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Adipocytes/*metabolism/pathology ; Adipokines/genetics/*metabolism ; Adipose Tissue/*metabolism/pathology ; Animals ; Dietary Fats/administration & dosage ; Dietary Sucrose/administration & dosage ; Fatty Liver/pathology/therapy ; Genetic Vectors ; Glucose/metabolism ; Humans ; Inflammation ; Insulin/metabolism ; Insulin Resistance ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism ; Macrophages/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Mitogen-Activated Protein Kinase 8/genetics/metabolism ; Obesity/*metabolism/pathology ; Phosphorylation ; Rats ; Rats, Zucker ; Signal Transduction ; Wnt Proteins/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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