Reciprocal Signaling between Heterotrimeric G Proteins and the p21-stimulated Protein Kinase*

p21-activated protein kinase (PAK)-1 phosphorylated Gαz, a member of the Gαi family that is found in the brain, platelets, and adrenal medulla. Phosphorylation approached 1 mol of phosphate/mol of Gαz in vitro. In transfected cells, Gαz was phosphorylated both by wild-type PAK1 when stimulated by the GTP-binding protein Rac1 and by constitutively active PAK1 mutants. In vitro, phosphorylation occurred only at Ser16, one of two Ser residues that are the major substrate sites for protein kinase C (PKC). PAK1 did not phosphorylate other Gα subunits (i1, i2, i3, o, s, or q). PAK1-phosphorylated Gαz was resistant both to RGSZ1, a Gz-selective GTPase-activating protein (GAP), and to RGS4, a relatively nonselective GAP for the Gi and Gqfamilies of G proteins. Phosphorylation of Ser27 by PKC did not alter sensitivity to either GAP. The previously described inhibition of Gz GAPs by PKC is therefore mediated by phosphorylation of Ser16. Phosphorylation of either Ser16 by PAK1 or Ser27 by PKC decreased the affinity of Gαz for Gβγ; phosphorylation of both residues by PKC caused no further effect. PAK1 thus regulates Gαz function by attenuating the inhibitory effects of both GAPs and Gβγ. In this context, the kinase activity of PAK1 toward several protein substrates was directly inhibited by Gβγ, suggesting that PAK1 acts as a Gβγ-regulated effector protein. This inhibition of mammalian PAK1 by Gβγ contrasts with the stimulation of the PAK homolog Ste20p in Saccharomyces cerevisiae by the Gβγ homolog Ste4p/Ste18p.

• Publication year

  1999

• Venue

  Journal of Biological Chemistry

• Publication date

  1999-10-29

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.274.44.31641PMID 10531372
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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