Role of the Bsk/Iyk non-receptor tyrosine kinase for the control of growth and hormone production in RINm5F cells.
Bsk/Iyk, a murine non-receptor-tyrosine kinase which is expressed in fetal and adult islet of Langerhans was previously found to decrease NIH3T3 cell proliferation when expressed as a Y497/504F-mutant. We presently wanted to determine the effects of Bsk/Iyk on the proliferation of insulin producing cells. Cells expressing Bsk/IykY497/504F and Bsk/IykY504F display a decreased proliferation rate and express higher levels of the cell cycle inhibitor p27/Kip1 compared to control cells. These mutants also conferred diminished cell viability in response to INF-gamma and IL-1beta and contain higher levels of glucagon mRNA. Wild-type Bsk/Iyk is mainly localized at the plasma membrane whereas mutant Bsk/Iyk can enter the nucleus. In vitro kinase reactions using an exogenous substrate indicate a complicated mode of regulation of kinase activity by Y497 and Y504 with the latter being homologous to Y527 in pp60c-Src. These findings suggest that Bsk/Iyk might play a role in inhibiting cell proliferation, transducing cytokine-induced cytotoxicity and regulating hormone production of endocrine pancreatic cells.
Annerén
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Department of Medical Cell Biology, Biomedicum Uppsala University, Sweden.
Welsh
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D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005934:Glucagon / Q000096:biosynthesis; D006728:Hormones / Q000096:biosynthesis*; D007328:Insulin / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009154:Mutation; D009363:Neoplasm Proteins; D010750:Phosphoproteins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D050717:Retinoblastoma-Like Protein p130; D013347:Subcellular Fractions / Q000201:enzymology; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D019061:src-Family Kinases
C493961:Cdkn1b protein, mouse; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D006728:Hormones; D007328:Insulin; D007375:Interleukin-1; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D050717:Retinoblastoma-Like Protein p130; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D007371:Interferon-gamma; D005934:Glucagon; C490511:Frk protein, rat; D011505:Protein-Tyrosine Kinases; C490512:Frk protein, mouse; D019061:src-Family Kinases