PMID- 10391677
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20181201
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 25
DP  - 1999 Jun 24
TI  - SHP-2 binds to Tyr763 and Tyr1009 in the PDGF beta-receptor and mediates
      PDGF-induced activation of the Ras/MAP kinase pathway and chemotaxis.
PG  - 3696-702
AB  - Activation of the beta-receptor for platelet-derived growth factor (PDGF) by its 
      ligand leads to autophosphorylation on a number of tyrosine residues. Here we
      show that Tyr763 in the kinase insert region is a novel autophosphorylation site,
      which after phosphorylation binds the protein tyrosine phosphatase SHP-2. SHP-2
      has also previously been shown to bind to phosphorylated Tyr1009 in the PDGF
      beta-receptor. Porcine aortic endothelial (PAE) cells transfected with a PDGF
      beta-receptor in which Tyr763 and Tyr1009 were mutated to phenylalanine residues 
      failed to associate with SHP-2 after ligand stimulation. Moreover,
      PDGF-BB-induced Ras GTP-loading and Erk2 activation were severely compromised in 
      the receptor mutant. Whereas the mitogenic response to PDGF-BB remained at the
      same level as in cells expressing wild-type PDGF beta-receptor, chemotaxis
      induced by PDGF-BB was significantly decreased in the case of the Y763F/Y1009F
      mutant cells, suggesting an important role for SHP-2 in chemotactic signaling.
FAU - Ronnstrand, L
AU  - Ronnstrand L
AD  - Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala, Sweden.
FAU - Arvidsson, A K
AU  - Arvidsson AK
FAU - Kallin, A
AU  - Kallin A
FAU - Rorsman, C
AU  - Rorsman C
FAU - Hellman, U
AU  - Hellman U
FAU - Engstrom, U
AU  - Engstrom U
FAU - Wernstedt, C
AU  - Wernstedt C
FAU - Heldin, C H
AU  - Heldin CH
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 1B56C968OA (Becaplermin)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
RN  - EC 2.7.10.1 (Receptors, Platelet-Derived Growth Factor)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (Ptpn11 protein, mouse)
RN  - EC 3.1.3.48 (Ptpn6 protein, mouse)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Becaplermin
MH  - Binding Sites
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism/*physiology
MH  - Cells, Cultured
MH  - *Chemotaxis
MH  - Endothelium, Vascular/metabolism
MH  - Enzyme Activation
MH  - Guanosine Triphosphate/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - *Protein Processing, Post-Translational
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/*metabolism
MH  - Proto-Oncogene Proteins c-sis
MH  - Receptor, Platelet-Derived Growth Factor beta
MH  - Receptors, Platelet-Derived Growth Factor/chemistry/*metabolism
MH  - *Signal Transduction
MH  - Swine
MH  - Transfection
MH  - Tyrosine/*metabolism
MH  - ras Proteins/*physiology
EDAT- 1999/07/03 00:00
MHDA- 1999/07/03 00:01
CRDT- 1999/07/03 00:00
PHST- 1999/07/03 00:00 [pubmed]
PHST- 1999/07/03 00:01 [medline]
PHST- 1999/07/03 00:00 [entrez]
AID - 10.1038/sj.onc.1202705 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jun 24;18(25):3696-702. doi: 10.1038/sj.onc.1202705.