Atypical protein kinase C (PKCζ/λ) is a convergent downstream target of the insulin-stimulated phosphatidylinositol 3-kinase and TC10 signaling pathways

Makoto Kanzaki, Silvia Mora, Joseph B. Hwang, Alan R. Saltiel, Jeffrey E. Pessin

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Insulin stimulation of adipocytes resulted in the recruitment of atypical PKC (PKCζ/λ) to plasma membrane lipid raft microdomains. This redistribution of PKCζ/λ was prevented by Clostridium difficile toxin B and by cholesterol depletion, but was unaffected by inhibition of phosphatidylinositol (PI) 3-kinase activity. Expression of the constitutively active GTP-bound form of TC10 (TC10Q/75L), but not the inactive GDP-bound mutant (TC10/T31N), targeted PKCζ/λ to the plasma membrane through an indirect association with the Par6-Par3 protein complex. In parallel, insulin stimulation as well as TC10/Q75L resulted in the activation loop phosphorylation of PKCζ. Although PI 3-kinase activation also resulted in PKCζ/λ phosphorylation, it was not recruited to the plasma membrane. Furthermore, insulin-induced GSK-3β phosphorylation was mediated by both PI 3-kinase-PKB and the TC10-Par6-atypical PKC signaling pathways. Together, these data demonstrate that PKCζ/λ can serve as a convergent downstream target for both the PI 3-kinase and TC10 signaling pathways, but only the TC10 pathway induces a spatially restricted targeting to the plasma membrane.

Original languageEnglish (US)
Pages (from-to)279-290
Number of pages12
JournalJournal of Cell Biology
Volume164
Issue number2
DOIs
StatePublished - Jan 19 2004
Externally publishedYes

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Phosphatidylinositol 3-Kinase
Protein Kinase C
Cell Membrane
Insulin
Phosphorylation
Glycogen Synthase Kinase 3
Membrane Lipids
Guanosine Triphosphate
Adipocytes
Cholesterol
PKC-3 protein
Proteins

Keywords

  • Adipocyte
  • Compartmentalization
  • Insulin
  • Lipid raft
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology

Cite this

Atypical protein kinase C (PKCζ/λ) is a convergent downstream target of the insulin-stimulated phosphatidylinositol 3-kinase and TC10 signaling pathways. / Kanzaki, Makoto; Mora, Silvia; Hwang, Joseph B.; Saltiel, Alan R.; Pessin, Jeffrey E.

In: Journal of Cell Biology, Vol. 164, No. 2, 19.01.2004, p. 279-290.

Research output: Contribution to journalArticle

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