Role of the Bsk/Iyk Non-Receptor Tyrosine Kinase for the Control of Growth and Hormone Production in RINm5F Cells

Growth Factors. 2000;17(4):233-47. doi: 10.3109/08977190009028969.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Southern
  • Cell Cycle / physiology
  • Cell Cycle Proteins*
  • Cell Division / physiology
  • Cell Survival / drug effects
  • Cyclin-Dependent Kinase Inhibitor p27
  • Glucagon / biosynthesis
  • Hormones / biosynthesis*
  • Insulin / biosynthesis
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Mice
  • Microtubule-Associated Proteins / biosynthesis
  • Mutation
  • Neoplasm Proteins*
  • Phosphoproteins / biosynthesis
  • Polymerase Chain Reaction
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proteins*
  • RNA, Messenger / metabolism
  • Rats
  • Retinoblastoma-Like Protein p130
  • Subcellular Fractions / enzymology
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*
  • src-Family Kinases

Substances

  • Cdkn1b protein, mouse
  • Cdkn1b protein, rat
  • Cell Cycle Proteins
  • Hormones
  • Insulin
  • Interleukin-1
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Phosphoproteins
  • Proteins
  • RNA, Messenger
  • Retinoblastoma-Like Protein p130
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Interferon-gamma
  • Glucagon
  • Frk protein, rat
  • Protein-Tyrosine Kinases
  • Frk protein, mouse
  • src-Family Kinases