RGD Reference Report - Regulation of protein kinase C zeta by PI 3-kinase and PDK-1. - Rat Genome Database

RGD Reference Report - Regulation of protein kinase C zeta by PI 3-kinase and PDK-1. - Rat Genome Database

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General

Regulation of protein kinase C zeta by PI 3-kinase and PDK-1.
Authors:	Chou, MM Hou, W Johnson, J Graham, LK Lee, MH Chen, CS Newton, AC Schaffhausen, BS Toker, A
Citation:	Chou MM, etal., Curr Biol. 1998 Sep 24;8(19):1069-77.
RGD ID:	1642663
Pubmed:	PMID:9768361 (View Abstract at PubMed)
BACKGROUND: Protein kinase C zeta (PKC zeta) is a member of the PKC family of enzymes and is involved in a wide range of physiological processes including mitogenesis, protein synthesis, cell survival and transcriptional regulation. PKC zeta has received considerable attention recently as a target of phosphoinositide 3-kinase (PI 3-kinase), although the mechanism of PKC zeta activation is, as yet, unknown. Recent reports have also shown that the phosphoinositide-dependent protein kinase-1 (PDK-1), which binds with high affinity to the PI 3-kinase lipid product phosphatidylinositol-3,4,5-trisphosphate (Ptdins-3,4,5-P3), phosphorylates and potently activates two other PI 3-kinase targets, the protein kinases Akt/PKB and p70S6K. We therefore investigated whether PDK-1 is the kinase that activates PKC zeta. RESULTS: In vivo, PI 3-kinase is both necessary and sufficient to activate PKC zeta. PDK-1 phosphorylates and activates PKC zeta in vivo, and we have shown that this is due to phosphorylation of threonine 410 in the PKC zeta activation loop. In vitro, PDK-1 phosphorylates and activates PKC zeta in a Ptdins-3,4,5-P3-enhanced manner. PKC zeta and PDK-1 are associated in vivo, and membrane targeting of PKC zeta renders it constitutively active in cells. CONCLUSIONS: Our results have identified PDK-1 as the kinase that phosphorylates and activates PKC zeta in the PI 3-kinase signaling pathway. This phosphorylation and activation of PKC zeta by PDK-1 is enhanced in the presence of Ptdins-3,4-5-P3. Consistent with the notion that PKCs are enzymes that are regulated at the plasma membrane, a membrane-targeted PKC zeta is constitutively active in the absence of agonist stimulation. The association between PKC zeta and PDK-1 reveals extensive cross-talk between enzymes in the PI 3-kinase signaling pathway.

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Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
protein kinase binding		IPI	PDK1 (Homo sapiens)	1642663		RGD

Objects Annotated

Genes (Rattus norvegicus)

Prkcz (protein kinase C, zeta)

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