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A direct interaction between JNK1 and CrkII is critical for Rac1‐induced JNK activation
Author(s) -
Girardin Stephen E.,
Yaniv Moshe
Publication year - 2001
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/20.13.3437
Subject(s) - signal transducing adaptor protein , microbiology and biotechnology , sh3 domain , biology , adapter molecule crk , signal transduction , proto oncogene tyrosine protein kinase src , kinase , rac1 , protein kinase a , phosphorylation
CrkII, a cellular homolog of v‐crk , belongs to a family of adaptor proteins that play a central role in signal transduction cascades. We demonstrate that CrkII interacts directly with c‐Jun N‐terminal kinase 1 (JNK1). A proline‐rich sequence of JNK1 is critical for the interaction of the kinase with the N‐terminal Src homology 3 (SH3) domain of CrkII. JNK1 is localized with CrkII in membrane ruffles of Crk‐overexpressing cells in a Rac1‐dependent manner. A JNK1 mutant (K340A) that fails to interact with CrkII is defective in Rac/epidermal growth factor‐induced activation, but remains responsive to UVC irradiation. Furthermore, CrkII recruits JNK1 to a p130Cas multiprotein complex where it may be activated through a hematopoietic progenitor kinase 1‐ and mitogen‐activated protein kinase kinase 4‐dependent pathway. Together, the results presented here argue for a new mechanism of regulation of the JNK pathway through the CrkII–p130Cas adaptor complex.