RGD Reference Report - Src tyrosine kinase regulates insulin-induced activation of protein kinase C (PKC) delta in skeletal muscle. - Rat Genome Database

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

Authors: Rosenzweig, T  Aga-Mizrachi, S  Bak, A  Sampson, SR 
Citation: Rosenzweig T, etal., Cell Signal. 2004 Nov;16(11):1299-308.
RGD ID: 2325149
Pubmed: PMID:15337529   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cellsig.2004.03.015   (Journal Full-text)

Insulin stimulation of skeletal muscle results in rapid activation of protein kinase Cdelta (PKCdelta), which is associated with its tyrosine phosphorylation and physical association with insulin receptor (IR). The mechanisms underlying tyrosine phosphorylation of PKCdelta 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 PKCdelta. Inhibition of Src by treatment with the Src family inhibitor PP2 reduced insulin-stimulated Src-PKCdelta association, PKCdelta tyrosine phosphorylation and PKCdelta activation. PP2 inhibition of Src also decreased insulin-induced IR tyrosine phosphorylation, IR-PKCdelta association and association of Src with both PKCdelta and IR. Finally, inhibition of Src decreased insulin-induced glucose uptake. We conclude that insulin activates Src tyrosine kinase, which regulates PKCdelta activity. Thus, Src tyrosine kinase may play an important role in insulin-induced tyrosine phosphorylation of both IR and PKCdelta. Moreover, both Src and PKCdelta appear to be involved in IR activation and subsequent downstream signaling.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PrkcdRatprotein kinase binding  IPISrc (Rattus norvegicus) RGD 
SrcRatprotein kinase C binding  IPIPrkcd (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkcd  (protein kinase C, delta)
Src  (SRC proto-oncogene, non-receptor tyrosine kinase)


Additional Information