RGD Reference Report - The regulatory domain of protein kinase C delta positively regulates insulin receptor signaling. - Rat Genome Database

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The regulatory domain of protein kinase C delta positively regulates insulin receptor signaling.

Authors: Jacob, AI  Horovitz-Fried, M  Aga-Mizrachi, S  Brutman-Barazani, T  Okhrimenko, H  Zick, Y  Brodie, C  Sampson, SR 
Citation: Jacob AI, etal., J Mol Endocrinol. 2010 Mar;44(3):155-69. Epub 2009 Dec 1.
RGD ID: 2325147
Pubmed: PMID:19952103   (View Abstract at PubMed)
DOI: DOI:10.1677/JME-09-0119   (Journal Full-text)

Protein kinase C delta (PKCdelta) is induced by insulin to rapidly associate with insulin receptor (IR) and upregulates insulin signaling. We utilized specific JM and CT receptor domains and chimeras of PKCalpha and PKCdelta regulatory and catalytic domains to elucidate which components of PKCdelta are responsible for positive regulatory effects of PKCdelta on IR signaling. Studies were performed on L6 and L8 skeletal muscle myoblasts and myotubes. PKCdelta was preferentially bound to the JM domain of IR, and insulin stimulation increased this binding. Both PKCdelta/alpha and PKCalpha/delta chimeras (regulatory/catalytic) were bound preferentially to the JM but not to the CT domain of IR. Although IR-PKCdelta binding was higher in cells expressing either the PKCdelta/alpha or PKCalpha/delta chimera than in control cells, upregulation of IR signaling was observed only in PKCdelta/alpha cells. Thus, in response to insulin increases in tyrosine phosphorylation of IR and insulin receptor substrate-1, downstream signaling to protein kinase B and glycogen synthase kinase 3 (GSK3) and glucose uptake were greater in cells overexpressing PKCdelta/alpha and the PKCdelta/delta domains than in cells expressing the PKCalpha/delta domains. Basal binding of Src to PKCdelta was higher in both PKCdelta/alpha- and PKCalpha/delta-expressing cells compared to control. Binding of Src to IR was decreased in PKCalpha/delta cells but remained elevated in the PKCdelta/alpha cells in response to insulin. Finally, insulin increased Src activity in PKCdelta/alpha-expressing cells but decreased it in PKCalpha/delta-expressing cells. Thus, the regulatory domain of PKCdelta via interaction with Src appears to determine the role of PKCdelta as a positive regulator of IR signaling in skeletal muscle.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to insulin stimulus  IEP 2325147 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Insr  (insulin receptor)
Prkce  (protein kinase C, epsilon)
Src  (SRC proto-oncogene, non-receptor tyrosine kinase)


Additional Information