PMID- 10970810
OWN - NLM
STAT- MEDLINE
DCOM- 20010118
LR  - 20181130
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 350 Pt 3
IP  - Pt 3
DP  - 2000 Sep 15
TI  - The beta-subunit of the hepatocyte growth factor/scatter factor (HGF/SF) receptor 
      phosphorylates and associates with CrkII: expression of CrkII enhances 
      HGF/SF-induced mitogenesis.
PG  - 925-32
AB  - CrkII, a 40 kDa adaptor possessing a Src homology (SH)2 domain followed by two 
      SH3 domains, although not endowed with catalytic activity, participates in 
      intracellular signalling, presumably by activating the Ras pathway. CrkII was 
      found to be phosphorylated in response to hepatocyte growth factor/scatter factor 
      (HGF/SF) and to associate with the beta-subunit of the HGF receptor (MET). CrkII 
      associated with p(145betaMET) via its SH2 domain. Growth-factor-receptor-bound 
      protein 2 (Grb2) co-immunoprecipitated with CrkII species. By transient 
      transfection of A431 human epidermoid carcinoma cells with wild-type and 
      dominant-negative Grb2 expression constructs lacking either the SH2 or SH3 
      domains, we have concluded that Grb2 does not contribute to the 'presentation' of 
      CrkII to p(145betaMET). Overexpression of wild-type CrkII in A431 cells enhanced 
      HGF/SF-induced proliferation, while a CrkII dominant-negative mutant lacking the 
      SH2 domain prevented a similar proliferating response to HGF/SF. The effect of 
      CrkII on HGF/SF-induced proliferation was also abolished in cells co-expressing 
      CrkII and Son-of-sevenless lacking the guanine exchange domain, suggesting that 
      CrkII is likely to induce cell proliferation partly via the Ras/mitogen-activated 
      protein kinase route.
FAU - Riordan, S M
AU  - Riordan SM
AD  - Laboratory of Cell Biology, Institute of Hepatology, Department of Medicine, 
      Royal Free and University College London Medical School, London WC1E 6HX, U.K.
FAU - Lidder, S
AU  - Lidder S
FAU - Williams, R
AU  - Williams R
FAU - Skouteris, G G
AU  - Skouteris GG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Androstadienes)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (GRB2 protein, human)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-crk)
RN  - 22144-77-0 (Cytochalasin D)
RN  - 42HK56048U (Tyrosine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.- (Protein Kinases)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Androstadienes/pharmacology
MH  - Cytochalasin D/pharmacology
MH  - GRB2 Adaptor Protein
MH  - Hepatocyte Growth Factor/chemistry/*metabolism/physiology
MH  - Humans
MH  - Mitosis/*physiology
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - Proteins/metabolism
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-crk
MH  - Tumor Cells, Cultured
MH  - Tyrosine/metabolism
MH  - Wortmannin
MH  - src Homology Domains
PMC - PMC1221328
EDAT- 2000/09/06 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/03/15
CRDT- 2000/09/06 11:00
PHST- 2000/09/06 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/06 11:00 [entrez]
PHST- 2001/03/15 00:00 [pmc-release]
PST - ppublish
SO  - Biochem J. 2000 Sep 15;350 Pt 3(Pt 3):925-32.