A direct interaction between JNK1 and CrkII is critical for Rac1-induced JNK activation.

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.
Mesh Terms:
Amino Acid Substitution, Binding Sites, Cell Membrane, Enzyme Activation, Epidermal Growth Factor, Hela Cells, Humans, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase 4, MAP Kinase Signaling System, Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase, Mitogen-Activated Protein Kinase 8, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Mutagenesis, Site-Directed, Protein Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-crk, Recombinant Proteins, Transfection, Ultraviolet Rays, rac1 GTP-Binding Protein, src Homology Domains
EMBO J.
Date: Jul. 02, 2001
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