Novel phosphorylation of c-ras p21 by protein kinases

P. Saikumar, L. S. Ulsh, D. J. Clanton, K. P. Huang

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Novel p21 phosphorylation was found in cells expressing high levels of this product of c-H- and c-K-ras genes. Phorbol 12,13-dibutyrate, a protein kinase C (PKC) activator, and permeable c-AMP derivatives, which activate protein kinase A (PKA), stimulated phosphorylation of K-ras(4B) p21 in 416B cells 3 to 5 fold. By tryptic peptide mapping, it was found that both PKC and PKA phosphorylated in vitro the K-ras p21 at the same site as was found in p21 from cells labeled with [32P]orthophosphate in vivo. A common site of H-ras p21 was also phosphorylated by both PKC and PKA, although phosphopeptides of H-ras p21 were distinct from those of K-ras p21. The construction of a mutant by site-directed mutagenesis allowed the identification of serine-177 as the phosphorylation site of H-ras p21. This novel phosphorylation site lies in the hypervariable region, which links the globular catalytic domain of p21 to the membrane-anchoring site at the C-terminus, a location suggesting that this phosphorylation plays a role in modulating transmembrane signaling.

Original languageEnglish (US)
Pages (from-to)213-222
Number of pages10
JournalOncogene Research
Volume3
Issue number3
StatePublished - Dec 1 1988
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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