PMID- 8302603
OWN - NLM
STAT- MEDLINE
DCOM- 19940304
LR  - 20220309
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 9
IP  - 1
DP  - 1994 Jan
TI  - Tyrosines1234-1235 are critical for activation of the tyrosine kinase encoded by 
      the MET proto-oncogene (HGF receptor).
PG  - 49-57
AB  - The tyrosine kinase encoded by the MET proto-oncogene (p190MET) is the receptor 
      for Hepatocyte Growth Factor/Scatter Factor (HGF/SF). Previous work has shown 
      that autophosphorylation of p190MET enhances its enzymatic activity and that the 
      major phosphorylation site is Tyr1235, located in the catalytic domain. This 
      residue is part of a 'three tyrosine' motif, including Tyr1230, Tyr1234, and 
      Tyr1235, conserved in several other receptor kinases. We studied the role of 
      these tyrosines in the positive regulation of the p190MET kinase by site-directed 
      mutagenesis. Substitution of either Tyr1235 or Tyr1234 with phenylalanine 
      severely reduced the in vitro kinase activity toward exogenous substrates. 
      Kinetic experiments showed that the residual activity of these mutants could 
      still be enhanced by autophosphorylation. Phosphopeptide mapping indicated that, 
      in the absence of Tyr1235, Tyr1234 is phosphorylated. Only the replacement of 
      both Tyr1234 and Tyr1235 yielded a mutant which completely lost the ability to be 
      activated by autophosphorylation. In stable transfectants expressing the HGF/SF 
      receptor with single substitution of either Tyr1234 or Tyr1235 the response to 
      HGF/SF was impaired. The ligand did not induce tyrosine phosphorylation of the 
      receptor nor stimulated chemotaxis. These data show that Tyr1234 and Tyr1235 are 
      critical for the activation of the HGF/SF receptor kinase both in vitro and in 
      response to the ligand in intact cells.
FAU - Longati, P
AU  - Longati P
AD  - Department of Biomedical Sciences and Oncology, University of Torino Medical 
      School, Italy.
FAU - Bardelli, A
AU  - Bardelli A
FAU - Ponzetto, C
AU  - Ponzetto C
FAU - Naldini, L
AU  - Naldini L
FAU - Comoglio, P M
AU  - Comoglio PM
LA  - eng
SI  - GENBANK/X76453
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
GS  - MET
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - Enzyme Activation
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-met
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Structure-Activity Relationship
MH  - Transfection
MH  - Tyrosine/metabolism
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
PST - ppublish
SO  - Oncogene. 1994 Jan;9(1):49-57.