PMID- 7687741
OWN - NLM
STAT- MEDLINE
DCOM- 19930824
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 13
IP  - 8
DP  - 1993 Aug
TI  - A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its 
      association with the hepatocyte growth factor/scatter factor receptor.
PG  - 4600-8
AB  - The pleiotropic effects (mitogenesis, motogenesis, and morphogenesis) elicited by 
      hepatocyte growth factor/scatter factor (HGF/SF) are mediated by the activation 
      of the tyrosine kinase receptor encoded by the MET proto-oncogene. Following 
      autophosphorylation, the receptor associates with the p85/110 
      phosphatidylinositol (PI) 3-kinase complex in vivo and in vitro. By a combination 
      of two complementary approaches, competition with synthetic phosphopeptides and 
      association with Tyr-Phe receptor mutants, we have identified Y-1349 and Y-1356 
      in the HGF/SF receptor as the binding sites for PI 3-kinase. Y-1349VHV and 
      Y-1356VNV do not conform to the canonical consensus sequence YXXM for PI 3-kinase 
      binding and thus define YVXV as a novel recognition motif. Y-1349 and Y-1356 are 
      located within the C-terminal portion of the HGF/SF receptor and are 
      phosphorylation sites. The affinity of the N- and C-terminal src homology region 
      2 (SH2) domains of p85 for the phosphopeptides including Y-1349 and Y-1356 is 2 
      orders of magnitude lower than that measured for Y-751 in the platelet-derived 
      growth factor receptor binding site. However, the closely spaced duplication of 
      the novel recognition motif in the native HGF/SF receptor may allow binding with 
      both SH2 domains of p85, thus generating an efficient docking site for PI 
      3-kinase. In agreement with this model, we have observed that a phosphopeptide 
      including both Y-1349 and Y-1356 activates PI 3-kinase in vitro.
FAU - Ponzetto, C
AU  - Ponzetto C
AD  - Department of Biomedical Sciences and Oncology, University of Turin, Italy.
FAU - Bardelli, A
AU  - Bardelli A
FAU - Maina, F
AU  - Maina F
FAU - Longati, P
AU  - Longati P
FAU - Panayotou, G
AU  - Panayotou G
FAU - Dhand, R
AU  - Dhand R
FAU - Waterfield, M D
AU  - Waterfield MD
FAU - Comoglio, P M
AU  - Comoglio PM
LA  - eng
SI  - GENBANK/X54559
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Peptides)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding, Competitive
MH  - Cloning, Molecular
MH  - Hepatocyte Growth Factor/*metabolism
MH  - In Vitro Techniques
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Peptides/metabolism
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphoproteins/metabolism
MH  - Phosphotransferases/*metabolism
MH  - Phosphotyrosine
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-met
MH  - Receptors, Cell Surface/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Signal Transduction
MH  - Tyrosine/analogs & derivatives/metabolism
PMC - PMC360084
EDAT- 1993/08/01 00:00
MHDA- 1993/08/01 00:01
PMCR- 1993/08/01
CRDT- 1993/08/01 00:00
PHST- 1993/08/01 00:00 [pubmed]
PHST- 1993/08/01 00:01 [medline]
PHST- 1993/08/01 00:00 [entrez]
PHST- 1993/08/01 00:00 [pmc-release]
AID - 10.1128/mcb.13.8.4600-4608.1993 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1993 Aug;13(8):4600-8. doi: 10.1128/mcb.13.8.4600-4608.1993.