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
(1999) In Oncogene 18(25). p.3696-3702- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1782672
- author
- Rönnstrand, Lars LU ; Arvidsson, Ann-Kristin ; Kallin, Anders ; Rorsman, Charlotte ; Hellman, Ulf ; Engström, Ulla ; Wernstedt, Christer and Heldin, Carl-Henrik
- publishing date
- 1999
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Non-Receptor Type 6 Protein Tyrosine Phosphatases/*metabolism Receptor, Platelet-Derived Growth Factor beta Receptors, Post-Translational Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatase, Site-Directed Phosphorylation Phosphotyrosine/metabolism Platelet-Derived Growth Factor/pharmacology *Protein Processing, Vascular/metabolism Enzyme Activation Guanosine Triphosphate/metabolism Intracellular Signaling Peptides and Proteins Mice Mitogen-Activated Protein Kinase 1 Molecular Sequence Data Mutagenesis, Cultured *Chemotaxis Endothelium, Amino Acid Sequence Animals Binding Sites Calcium-Calmodulin-Dependent Protein Kinases/metabolism/*physiology Cells, Platelet-Derived Growth Factor/chemistry/*metabolism *Signal Transduction Swine Transfection Tyrosine/*metabolism ras Proteins/*physiology
- in
- Oncogene
- volume
- 18
- issue
- 25
- pages
- 3696 - 3702
- publisher
- Nature Publishing Group
- ISSN
- 1476-5594
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
- id
- fa3b48cc-750e-45cf-ad1b-45a656793a0b (old id 1782672)
- date added to LUP
- 2016-04-04 08:53:49
- date last changed
- 2019-05-22 02:18:28
@article{fa3b48cc-750e-45cf-ad1b-45a656793a0b, abstract = {{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.}}, author = {{Rönnstrand, Lars and Arvidsson, Ann-Kristin and Kallin, Anders and Rorsman, Charlotte and Hellman, Ulf and Engström, Ulla and Wernstedt, Christer and Heldin, Carl-Henrik}}, issn = {{1476-5594}}, keywords = {{Non-Receptor Type 6 Protein Tyrosine Phosphatases/*metabolism Receptor; Platelet-Derived Growth Factor beta Receptors; Post-Translational Protein Tyrosine Phosphatase; Non-Receptor Type 11 Protein Tyrosine Phosphatase; Site-Directed Phosphorylation Phosphotyrosine/metabolism Platelet-Derived Growth Factor/pharmacology *Protein Processing; Vascular/metabolism Enzyme Activation Guanosine Triphosphate/metabolism Intracellular Signaling Peptides and Proteins Mice Mitogen-Activated Protein Kinase 1 Molecular Sequence Data Mutagenesis; Cultured *Chemotaxis Endothelium; Amino Acid Sequence Animals Binding Sites Calcium-Calmodulin-Dependent Protein Kinases/metabolism/*physiology Cells; Platelet-Derived Growth Factor/chemistry/*metabolism *Signal Transduction Swine Transfection Tyrosine/*metabolism ras Proteins/*physiology}}, language = {{eng}}, number = {{25}}, pages = {{3696--3702}}, publisher = {{Nature Publishing Group}}, series = {{Oncogene}}, title = {{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}}, volume = {{18}}, year = {{1999}}, }