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Stimulation of phospholipase C‐β 2 by the Rho GTPases Cdc42Hs and Rac1
Author(s) -
Illenberger Daria,
Schwald Frieder,
Pimmer Dominik,
Binder Wolfhard,
Maier Gernot,
Dietrich Alexander,
Gierschik Peter
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.21.6241
Subject(s) - biology , rac1 , stimulation , microbiology and biotechnology , gtpase , phospholipase d , neuroscience , signal transduction
Neutrophils contain a soluble guanine‐nucleotidebinding protein, made up of two components with molecular masses of 23 and 26 kDa, that mediates stimulation of phospholipase C‐β 2 (PLCβ 2 ). We have identified the two components of the stimulatory heterodimer by amino acid sequencing as a Rho GTPase and the Rho guanine nucleotide dissociation inhibitor LyGDI. Using recombinant Rho GTPases and LyGDI, we demonstrate that PLCβ 2 is stimulated by guanosine 5′‐ O ‐(3‐thiotriphosphate) (GTP[S])‐activated Cdc42Hs×LyGDI, but not by RhoA×LyGDI. Stimulation of PLCβ 2 , which was also observed for GTP[S]‐activated recombinant Rac1, was independent of LyGDI, but required C‐terminal processing of Cdc42Hs/Rac1. Cdc42Hs/Rac1 also stimulated PLCβ 2 in a system made up of purified recombinant proteins, suggesting that this function is mediated by direct protein–protein interaction. The Cdc42Hs mutants F37A and Y40C failed to stimulate PLCβ 2 , indicating that the Cdc42Hs effector site is involved in this interaction. The results identify PLCβ 2 as a novel effector of the Rho GTPases Cdc42Hs and Rac1, and as the first mammalian effector directly regulated by both heterotrimeric and low‐molecular‐mass GTP‐binding proteins.