Home LiteratureArticle Details
PMID: 11432831 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 20 ·No. 13 ·2001-07-02 ·Pages 3437-46

Girardin SE, Yaniv M

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.

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,radiation effects Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase Mitogen-Activated Protein Kinase 8 Mitogen-Activated Protein Kinase Kinases/metabolism Mitogen-Activated Protein Kinases/chemistry,genetics,metabolism Mutagenesis, Site-Directed Protein Kinases/chemistry,metabolism Proto-Oncogene Proteins Proto-Oncogene Proteins c-crk Recombinant Proteins/chemistry,metabolism Transfection Ultraviolet Rays rac1 GTP-Binding Protein/metabolism src Homology Domains
Chemicals
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
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Girardin S E
Unité des Virus Oncogènes, URA CNRS 1644, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris Cedex 15, France.
Yaniv M
References (46)
46 references, click to expand
  1. Growth hormone stimulates the formation of a multiprotein signaling complex involving p130(Cas) and CrkII. Resultant activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK).
    J Biol Chem. 1998 Dec 11;273(50):33864-75 PMID: 9837978
  2. Activation of Rac1 by a Crk SH3-binding protein, DOCK180.
    Genes Dev. 1998 Nov 1;12(21):3331-6 PMID: 9808620
  3. Interaction of hematopoietic progenitor kinase 1 with adapter proteins Crk and CrkL leads to synergistic activation of c-Jun N-terminal kinase.
    Mol Cell Biol. 1999 Feb;19(2):1359-68 PMID: 9891069
  4. The functional role of CrkII in actin cytoskeleton organization and mitogenesis.
    J Biol Chem. 1999 Jan 29;274(5):3001-8 PMID: 9915838
  5. Mitogen-activated protein kinases: specific messages from ubiquitous messengers.
    Mol Cell Biol. 1999 Apr;19(4):2435-44 PMID: 10082509
  6. Physiological signals and oncogenesis mediated through Crk family adapter proteins.
    J Cell Physiol. 1998 Dec;177(4):535-52 PMID: 10092207
  7. Signal transduction by the c-Jun N-terminal kinase.
    Biochem Soc Symp. 1999;64:1-12 PMID: 10207617
  8. Organization and regulation of mitogen-activated protein kinase signaling pathways.
    Curr Opin Cell Biol. 1999 Apr;11(2):211-8 PMID: 10209154
  9. Signal transduction pathways regulated by the Rho family of small GTPases.
    Br J Cancer. 1999 Jul;80 Suppl 1:25-7 PMID: 10466757
  10. The JIP group of mitogen-activated protein kinase scaffold proteins.
    Mol Cell Biol. 1999 Oct;19(10):7245-54 PMID: 10490659
  11. Signaling to Rho GTPases.
    Exp Cell Res. 1999 Nov 25;253(1):166-79 PMID: 10579921
  12. Crk activation of JNK via C3G and R-Ras.
    J Biol Chem. 2000 Apr 28;275(17):12667-71 PMID: 10777559
  13. Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase.
    J Cell Biol. 2000 May 1;149(3):741-54 PMID: 10791986
  14. Two species of human CRK cDNA encode proteins with distinct biological activities.
    Mol Cell Biol. 1992 Aug;12(8):3482-9 PMID: 1630456
  15. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.
    Cell. 1992 Aug 7;70(3):401-10 PMID: 1643658
  16. A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner.
    EMBO J. 1994 Aug 15;13(16):3748-56 PMID: 8070403
  17. Four proline-rich sequences of the guanine-nucleotide exchange factor C3G bind with unique specificity to the first Src homology 3 domain of Crk.
    J Biol Chem. 1994 Dec 30;269(52):32781-7 PMID: 7806500
  18. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation.
    Cell. 1995 Jan 27;80(2):179-85 PMID: 7834738
  19. SH2 and SH3 domains as molecular adhesives: the interactions of Crk and Abl.
    Trends Biochem Sci. 1994 Nov;19(11):453-8 PMID: 7855886
  20. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia.
    Cell. 1995 Apr 7;81(1):53-62 PMID: 7536630
  21. Cellular proteins binding to the first Src homology 3 (SH3) domain of the proto-oncogene product c-Crk indicate Crk-specific signaling pathways.
    Oncogene. 1995 Apr 20;10(8):1465-73 PMID: 7731701
  22. Affinity and specificity requirements for the first Src homology 3 domain of the Crk proteins.
    EMBO J. 1995 May 15;14(10):2191-8 PMID: 7774577
  23. How MAP kinases are regulated.
    J Biol Chem. 1995 Jun 23;270(25):14843-6 PMID: 7797459
  24. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway.
    Cell. 1995 Jun 30;81(7):1137-46 PMID: 7600581
  25. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs.
    Cell. 1995 Jun 30;81(7):1147-57 PMID: 7600582
  26. The regulation of AP-1 activity by mitogen-activated protein kinases.
    J Biol Chem. 1995 Jul 14;270(28):16483-6 PMID: 7622446
  27. DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane.
    Mol Cell Biol. 1996 Apr;16(4):1770-6 PMID: 8657152
  28. Selective interaction of JNK protein kinase isoforms with transcription factors.
    EMBO J. 1996 Jun 3;15(11):2760-70 PMID: 8654373
  29. Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins.
    J Biol Chem. 1996 Jun 14;271(24):14468-72 PMID: 8662907
  30. Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase/stress-activated protein kinase pathway. A role for mixed lineage kinase 3/protein-tyrosine kinase 1, a novel member of the mixed lineage kinase family.
    J Biol Chem. 1996 Nov 1;271(44):27225-8 PMID: 8910292
  31. Emerging components of the Crk oncogene product: the first identified adaptor protein.
    Cell Signal. 1996 Aug;8(5):335-40 PMID: 8911681
  32. Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton.
    Curr Opin Cell Biol. 1997 Feb;9(1):86-92 PMID: 9013670
  33. Mitogen-activated protein kinase pathways.
    Curr Opin Cell Biol. 1997 Apr;9(2):180-6 PMID: 9069255
  34. Downstream of Crk adaptor signaling pathway: activation of Jun kinase by v-Crk through the guanine nucleotide exchange protein C3G.
    Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2356-61 PMID: 9122199
  35. A cytoplasmic inhibitor of the JNK signal transduction pathway.
    Science. 1997 Aug 1;277(5326):693-6 PMID: 9235893
  36. Evidence for functional roles of Crk-II in insulin and epidermal growth factor signaling in Rat-1 fibroblasts overexpressing insulin receptors.
    Endocrinology. 1997 Nov;138(11):4950-8 PMID: 9348226
  37. Guanine-nucleotide exchange protein C3G activates JNK1 by a ras-independent mechanism. JNK1 activation inhibited by kinase negative forms of MLK3 and DLK mixed lineage kinases.
    J Biol Chem. 1998 Jan 16;273(3):1281-4 PMID: 9430657
  38. CAS/Crk coupling serves as a "molecular switch" for induction of cell migration.
    J Cell Biol. 1998 Feb 23;140(4):961-72 PMID: 9472046
  39. Signal transduction through MAP kinase cascades.
    Adv Cancer Res. 1998;74:49-139 PMID: 9561267
  40. Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to development.
    Curr Opin Cell Biol. 1998 Apr;10(2):205-19 PMID: 9561845
  41. Role of Crk oncogene product in physiologic signaling.
    Crit Rev Oncog. 1997;8(4):329-42 PMID: 9622053
  42. Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor.
    J Biol Chem. 1998 Jul 3;273(27):17186-91 PMID: 9642287
  43. A mammalian scaffold complex that selectively mediates MAP kinase activation.
    Science. 1998 Sep 11;281(5383):1671-4 PMID: 9733513
  44. Evidence that DOCK180 up-regulates signals from the CrkII-p130(Cas) complex.
    J Biol Chem. 1998 Sep 18;273(38):24479-84 PMID: 9733740
  45. Stress-activated protein kinases are negatively regulated by cell density.
    EMBO J. 1998 Oct 1;17(19):5615-26 PMID: 9755162
  46. The adaptor protein Crk connects multiple cellular stimuli to the JNK signaling pathway.
    Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15394-9 PMID: 9860979
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.13.3437
Published
2001-07-02
Pages
3437-46
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125507
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.13.3437 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2