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

EMBO J. 2001 Jul 2;20(13):3437-46. doi: 10.1093/emboj/20.13.3437.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Binding Sites
  • Cell Membrane / enzymology
  • Enzyme Activation
  • Epidermal Growth Factor / pharmacology
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • MAP Kinase Signaling System / physiology*
  • MAP Kinase Signaling System / radiation effects
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase*
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / chemistry
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mutagenesis, Site-Directed
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins c-crk
  • Proto-Oncogene Proteins*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Transfection
  • Ultraviolet Rays
  • rac1 GTP-Binding Protein / metabolism*
  • src Homology Domains

Substances

  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • Recombinant Proteins
  • Epidermal Growth Factor
  • Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
  • rac1 GTP-Binding Protein