Distinctive regulation of v-Src-associated phosphatidylinositol 3-kinase during PC12 cell differentiation

B Haefner, M C Frame

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

In chicken embryo fibroblasts, the binding of v-Src to PtdIns 3-kinase requires Src homology domains, SH3, SH2 and the SH1 or kinase domain, which induces the cytoskeletal disruption associated with fibroblast transformation. In the rat phaeochromocytoma PC12 cell line, v-Src has a different effect on the cytoskeleton, inducing neurite extension rather than cytoskeletal disruption. Here we show that v-Src-induced neurite outgrowth is suppressed by the selective PtdIns 3-kinase inhibitor LY294002, suggesting that this effect of v-Src in PC12 cells also requires the activity of the lipid kinase. However, in contrast with chicken embryo fibroblasts, the association of PtdIns 3-kinase with v-Src in PC12 cells is delayed until several hours after activating the v-Src tyrosine kinase. Furthermore the v-Src-associated p85 regulatory subunit of PtdIns 3-kinase is not phosphorylated on tyrosine in PC12 cells and associates only weakly with isolated v-Src homology domains (SH3/SH2) in a Src kinase-independent manner. However, p85 and v-Src both associate with an unidentified protein (of molecular mass approx. 68 kDa; termed p68), which becomes tyrosine phosphorylated concomitantly with the association of both p85 and PtdIns 3-kinase with v-Src in PC12 cells. Thus we conclude that the mode of regulation of v-Src-associated PtdIns 3-kinase is cell-context-dependent and that p68 might act as an adaptor protein to mediate the association of p85 and v-Src in PC12 cells. The different regulation of PtdIns 3-kinase in PC12 and in chicken embryo fibroblasts in response to v-Src activity might reflect the different cytoskeletal rearrangements induced by this oncoprotein in the two cell types.
Original languageEnglish
Pages (from-to)649-55
Number of pages7
JournalBiochemical Journal
Volume328 ( Pt 2)
Publication statusPublished - 1 Dec 1997

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Chromones
  • Enzyme Inhibitors
  • Fibroblasts
  • Gene Expression Regulation
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Models, Biological
  • Morpholines
  • Neurites
  • Oncogene Protein pp60(v-src)
  • PC12 Cells
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins
  • Phosphotyrosine
  • Protein Binding
  • Rats
  • src Homology Domains

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