Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71 of Rac1

Taegun Kwon, Do Yoon Kwon, Jaesun Chun, Jae-Hong Kim, Sang Sun Kang

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

A putative Akt kinase phosphorylation site (64ydRIR-plSYp73) was found in Rac1/CDC42 and Rho family proteins (RhoA, RhoB, RhoC, and RhoG). Phosphorylation of Rac1 by Akt kinase was assayed with recombinant Rac1 protein and the fluorescein-labeled Rac1 peptide. It was shown that the Rac1 peptide and the recombinant protein were phosphorylated by the activated recombinant Akt kinase and the lysate of SK-MEL28 cells, a human melanoma cell line. The phosphorylation of Rac1 inhibited its GTP-binding activity without any significant change in GTPase activity. Both the GTP-binding and GTPase activities of Racl S71A protein (with the serine residue to be phosphorylated replaced with alanine) were abolished regardless of the treatment of Akt kinase. Akt kinase activity and Rac1 peptide phosphorylation were down-regulated by the treatment of SK-MEL28 cells with wortmannin or LY294002 (a phosphoinositide 3-kinase inhibitor), but JNK/SAPK kinase activity was up-regulated. Thus, the results suggest that Akt kinase of the phosphoinositide 3-kinase signal transduction pathway phosphorylates serine 71 of Rac1 as one of its authentic substrates and modulates the Rac1 signal transduction pathway through phosphorylation.

Original languageEnglish
Pages (from-to)423-428
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number1
DOIs
Publication statusPublished - 2000 Jan 7
Externally publishedYes

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Phosphorylation
Guanosine Triphosphate
Protein Kinases
Serine
Phosphotransferases
1-Phosphatidylinositol 4-Kinase
GTP Phosphohydrolases
Recombinant Proteins
rhoB GTP-Binding Protein
Signal transduction
Peptides
Signal Transduction
rac1 GTP-Binding Protein
rhoA GTP-Binding Protein
MAP Kinase Kinase 4
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Fluorescein
Recombinant proteins
Alanine
Melanoma

ASJC Scopus subject areas

  • Biochemistry

Cite this

Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71 of Rac1. / Kwon, Taegun; Kwon, Do Yoon; Chun, Jaesun; Kim, Jae-Hong; Kang, Sang Sun.

In: Journal of Biological Chemistry, Vol. 275, No. 1, 07.01.2000, p. 423-428.

Research output: Contribution to journalArticle

Kwon, Taegun ; Kwon, Do Yoon ; Chun, Jaesun ; Kim, Jae-Hong ; Kang, Sang Sun. / Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71 of Rac1. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 1. pp. 423-428.
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