Common and distinct elements in insulin and PDGF signaling

M. G. Myers, B. Cheatham, T. L. Fisher, B. R. Jachna, C. R. Kahn, Jonathan M. Backer, M. F. White

Research output: Contribution to journalArticle

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Abstract

The receptors for insulin and PDGF are tyrosine kinases that mediate distinct effects in identical cellular backgrounds. Each receptor must therefore engage a unique subset of the available signaling elements-at least partly through the selection of proteins with src-homology 2 domains (SH2 proteins). Autophosphorylation sites in the PDGFr directly bind SH2 proteins, whereas activation of the insulin receptor leads to phosphorylation of IRS-1, which in turn binds SH2 proteins. In HIR 3.5 cells, which contain similar numbers of PDGF and insulin receptors, insulin, but not PDGF, stimulated tyrosyl phosphorylation of IRS-1. Similarly, insulin, but not PDGF, treatment of HIR 3.5 stimulated the association of IRS-1 with PtdIns 3'-kinase, although PDGF stimulated the association of PtdIns S'-kinase with the tyrosine-phosphorylated PDGFr. Association with IRS-1 activated PtdIns 3'-kinase more effectively than association with the PDGFr. Whereas the PDGFr associated with PtdIns 3'-kinase, ras-GAP, GRB-2, and phospholipase Cγ, only GRB-2 and PtdIns 3'-kinase associated with IRS-1. Moreover, PDGF, but not insulin, caused tyrosine phosphorylation of phospholipase Cγ in HIR 3.5 cells. Thus, the insulin signal differs from that of PDGF by the insertion of a cytosolic, nonreceptor SH2 domain docking protein (IRS-1). Furthermore, IRS-1 binds a different subset of SH2 domain-containing proteins than does the PDGFr and regulates at least one common element (PtdIns 3'-kinase) differently than the PDGFr. These results support the hypothesis that IRS-1 differentiates the signals generated by the insulin receptor and PDGFr tyrosine kinases by binding and regulating a specific subset of SH2 domain-containing signaling molecules.

Original languageEnglish (US)
Pages (from-to)369-387
Number of pages19
JournalAnnals of the New York Academy of Sciences
Volume766
DOIs
StatePublished - 1995

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Phosphatidylinositol 3-Kinases
src Homology Domains
Insulin
Phosphorylation
Insulin Receptor
Platelet-Derived Growth Factor Receptors
Proteins
Association reactions
Type C Phospholipases
Tyrosine
ras GTPase-Activating Proteins
Phosphatidylinositols
Protein-Tyrosine Kinases
Phosphotransferases
Chemical activation
Protein
Molecules
insulin receptor tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Myers, M. G., Cheatham, B., Fisher, T. L., Jachna, B. R., Kahn, C. R., Backer, J. M., & White, M. F. (1995). Common and distinct elements in insulin and PDGF signaling. Annals of the New York Academy of Sciences, 766, 369-387. https://doi.org/10.1111/j.1749-6632.1995.tb26687.x

Common and distinct elements in insulin and PDGF signaling. / Myers, M. G.; Cheatham, B.; Fisher, T. L.; Jachna, B. R.; Kahn, C. R.; Backer, Jonathan M.; White, M. F.

In: Annals of the New York Academy of Sciences, Vol. 766, 1995, p. 369-387.

Research output: Contribution to journalArticle

Myers, M. G. ; Cheatham, B. ; Fisher, T. L. ; Jachna, B. R. ; Kahn, C. R. ; Backer, Jonathan M. ; White, M. F. / Common and distinct elements in insulin and PDGF signaling. In: Annals of the New York Academy of Sciences. 1995 ; Vol. 766. pp. 369-387.
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