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A new Rac target POSH is an SH3‐containing scaffold protein involved in the JNK and NF‐κB signalling pathways
Author(s) -
Tapon Nicolas,
Nagata Kohichi,
Lamarche Nathalie,
Hall Alan
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/17.5.1395
Subject(s) - biology , oncogene , signal transduction , cell , microbiology and biotechnology , cell cycle , genetics
The Rho, Rac and Cdc42 GTPases coordinately regulate the organization of the actin cytoskeleton and the JNK MAP kinase pathway. Mutational analysis of Rac has previously shown that these two activities are mediated by distinct cellular targets, though their identity is not known. Two Rac targets, p65 PAK and MLK, are ser/thr kinases that have been reported to be capable of activating the JNK pathway. We present evidence that neither is the Rac target mediating JNK activation in Cos‐1 cells. We have used yeast two‐hybrid selection and identified a new target of Rac, POSH. This protein consists of four SH3 domains and ectopic expression leads to the activation of the JNK pathway and to nuclear translocation of NF‐κB. When overexpressed in fibroblasts, POSH is a strong inducer of apoptosis. We propose that POSH acts as a scaffold protein and contributes to Rac‐induced signal transduction pathways leading to diverse gene transcriptional changes.