Src tyrosine kinase regulates insulin-induced activation of protein kinase C (PKC) δ in skeletal muscle

Tovit Rosenzweig, Shlomit Aga-Mizrachi, Asia Bak, Sanford R. Sampson

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Insulin stimulation of skeletal muscle results in rapid activation of protein kinase Cδ (PKCδ), which is associated with its tyrosine phosphorylation and physical association with insulin receptor (IR). The mechanisms underlying tyrosine phosphorylation of PKCδ have not been determined. In this study, we investigated the possibility that the Src family of nonreceptor tyrosine kinases may be involved upstream insulin signaling. Studies were done on differentiated rat skeletal myotubes in primary culture. Insulin caused an immediate stimulation of Src and induced its physical association with both IR and PKCδ. Inhibition of Src by treatment with the Src family inhibitor PP2 reduced insulin-stimulated Src-PKCδ association, PKCδ tyrosine phosphorylation and PKCδ activation. PP2 inhibition of Src also decreased insulin-induced IR tyrosine phosphorylation, IR-PKCδ association and association of Src with both PKCδ and IR. Finally, inhibition of Src decreased insulin-induced glucose uptake. We conclude that insulin activates Src tyrosine kinase, which regulates PKCδ activity. Thus, Src tyrosine kinase may play an important role in insulin-induced tyrosine phosphorylation of both IR and PKCδ. Moreover, both Src and PKCδ appear to be involved in IR activation and subsequent downstream signaling.

Original languageEnglish
Pages (from-to)1299-1308
Number of pages10
JournalCellular Signalling
Volume16
Issue number11
DOIs
StatePublished - Nov 2004

Bibliographical note

Funding Information:
This research was supported in part by the Sorrell Foundation, the Ben and Effie Raber Research Fund and grant from The Israel Science Foundation founded by the Israel Academy of Sciences and Humanities, and from the Israel Ministry of Health.

Keywords

  • Glucose uptake
  • PKC
  • Skeletal muscle
  • Tyrosine kinase
  • Tyrosine phosphorylation

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