title: Growth hormone-induced reorganization of the actin cytoskeleton is not required for STAT5 (signal transducer and activator of transcription-5)-mediated transcription.
abstract: We have investigated the effect of GH on the organization of the actin cytoskeleton within the cell. Human GH (hGH) treatment (50 nM) of Chinese hamster ovary (CHO) cells stably transfected with the complementary DNA for the rat GH receptor (CHO-GHR(1-638)) resulted in a reorganization of actin filaments in the cell that was not observed upon GH treatment of the untransfected parental CHO cell line. hGH initially induced depolymerization of actin stress fibers similar in magnitude to that induced by treatment of the cells with 100 nM human insulin-like growth factor I. This loss of stress fibers was observed as early as 30 sec after addition of hGH to the medium, and maximal depolymerization of stress fibers was observed between 1-4 min after addition of hGH. This was followed by a slow, but submaximal, repolymerization of the stress fibers and the formation of localized focal filamentous actin containing complexes. Similar cytoskeletal changes were observed after hGH treatment in Swiss 3T3 fibroblasts and BRL cells stably transfected with rat GH receptor complementary DNA (BRL-GHR(1-6381)). Pretreatment of CHO-GHR(1-638) cells with wortmannin (a phosphatidylinositol 3-kinase inhibitor) and verapamil (a calcium channel antagonist) both inhibited the hGH-induced actin reorganization. The integrity of the actin cytoskeleton was not required for GH-induced STAT5 (signal transducer and activator of transcription-5)-mediated transcription, as treatment of cells with cytochalasins B and D did not alter the fold stimulation of the STAT5-mediated transcriptional response to GH. We conclude that GH induces a rapid reorganization of the actin cytoskeleton by a process requiring phosphatidylinositol 3-kinase activation and calcium influx, but this cytoskeletal reorganization is not required for the STAT5-mediated transcriptional response to GH.
authors.affiliation: Institute of Molecular and Cell Biology and Defense Medical Research Institute, National University of Singapore, Republic of Singapore.
authors.forename: E L
authors.initials: EL
authors.lastname: Goh
authors.forename: T J
authors.initials: TJ
authors.lastname: Pircher
authors.forename: T J
authors.initials: TJ
authors.lastname: Wood
authors.forename: G
authors.initials: G
authors.lastname: Norstedt
authors.forename: R
authors.initials: R
authors.lastname: Graichen
authors.forename: P E
authors.initials: PE
authors.lastname: Lobie
mesh_terms: D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D008854:Microscopy, Electron; D008894:Milk Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D051381:Rats; D011986:Receptors, Somatotropin / Q000235:genetics; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection; D014700:Verapamil / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D000199:Actins; D000730:Androstadienes; D002121:Calcium Channel Blockers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D014700:Verapamil; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000077191:Wortmannin