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http://purl.uniprot.org/citations/9768361http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9768361http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9768361http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.org/dc/terms/identifier"doi:10.1016/s0960-9822(98)70444-0"xsd:string
http://purl.uniprot.org/citations/9768361http://purl.org/dc/terms/identifier"doi:10.1016/s0960-9822(98)70444-0"xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Hou W."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Hou W."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Johnson J."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Johnson J."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Lee M.H."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Lee M.H."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Toker A."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Toker A."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Chen C.S."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Chen C.S."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Newton A.C."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Newton A.C."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Schaffhausen B.S."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Schaffhausen B.S."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Chou M.M."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Chou M.M."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Graham L.K."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/author"Graham L.K."xsd:string
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9768361http://purl.uniprot.org/core/date"1998"xsd:gYear
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