PMID- 7838524
OWN - NLM
STAT- MEDLINE
DCOM- 19950227
LR  - 20181130
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 10
IP  - 2
DP  - 1995 Jan 19
TI  - Efficient cell transformation by the Tpr-Met oncoprotein is dependent upon 
      tyrosine 489 in the carboxy-terminus.
PG  - 237-49
AB  - The receptor for hepatocyte growth factor/scatter factor (HGF/SF) was originally 
      identified as an oncogene, Tpr-Met, which consists of the cytoplasmic tyrosine 
      kinase domain of the HGF/SF receptor (Met) fused down-stream of sequences encoded 
      by the tpr gene. As a consequence of this rearrangement the Tpr-Met fusion 
      oncoprotein is localized to the cytoplasm and is a constitutively activated 
      kinase. To identify signalling pathways important for Tpr-Met-mediated cell 
      transformation we have generated tyrosine to phenylalanine mutants of Tpr-Met 
      that are compromised in their ability to transform Fischer rat 3T3 (Fr3T3) cells 
      in culture. We show that a single tyrosine residue in the carboxy terminus of 
      Tpr-Met (residue 489) is essential for efficient transformation of Fr3T3 cells by 
      this oncoprotein. Mutation of tyrosine 489 to phenylalanine does not affect the 
      exogenous kinase activity of the Tpr-Met oncoprotein toward casein, but it 
      impairs the ability of the mutant protein to bind to and activate 
      phosphatidylinositol 3 kinase in vivo and completely abolishes the in vivo 
      association with the Grb2 adaptor protein as well as the association and/or 
      phosphorylation of an unknown protein of 110 kDa. These data are consistent with 
      a single tyrosine residue in the Tpr-Met oncoprotein being essential for the 
      activation of several signalling pathways which lead to the transformation of 
      Fr3T3 fibroblasts.
FAU - Fixman, E D
AU  - Fixman ED
AD  - Royal Victoria Hospital, Department of Medicine, McGill University, Montreal, 
      Quebec, Canada.
FAU - Naujokas, M A
AU  - Naujokas MA
FAU - Rodrigues, G A
AU  - Rodrigues GA
FAU - Moran, M F
AU  - Moran MF
FAU - Park, M
AU  - Park M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Caseins)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (Grb2 protein, rat)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.67 (1-Phosphatidylinositol 4-Kinase)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - 1-Phosphatidylinositol 4-Kinase
MH  - *Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Caseins/metabolism
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Cells, Cultured
MH  - ErbB Receptors/metabolism
MH  - GRB2 Adaptor Protein
MH  - Hepatocyte Growth Factor/*physiology
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins/*physiology
MH  - Proto-Oncogene Proteins c-met
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/*physiology
MH  - Tyrosine/*physiology
EDAT- 1995/01/19 00:00
MHDA- 1995/01/19 00:01
CRDT- 1995/01/19 00:00
PHST- 1995/01/19 00:00 [pubmed]
PHST- 1995/01/19 00:01 [medline]
PHST- 1995/01/19 00:00 [entrez]
PST - ppublish
SO  - Oncogene. 1995 Jan 19;10(2):237-49.