| Structural highlights
Function
[PTN11_MOUSE] Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity (By similarity).[1] [PGFRB_MOUSE] Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM (By similarity). Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor.[2] [3] [4] [5] [6] [7] [8] [9] [10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: Src homology 2 (SH2) domains bind to phosphotyrosine residues in a sequence-specific manner, and thereby couple tyrosine phosphorylation to changes in the localization or catalytic activity of signal transducing molecules. Current understanding of SH2 specificity is based on the structures of SH2-peptide complexes of the closely-related Src and Lck tyrosine kinases. The tyrosine phosphatase Syp contains two SH2 domains that are relatively divergent from those of the tyrosine kinases, with distinct target specificities, and is thus well suited for structural studies aimed at extending our understanding of SH2 specificity. RESULTS: Crystal structures of the amino-terminal SH2 domain of Syp in separate complexes with two high-affinity peptides, in complex with a non-specific peptide and in the uncomplexed form have been determined at between 2 A and 3 A resolution. The structure of the SH2 domain and the mode of high-affinity peptide binding is essentially similar to that seen in the Src and Lck structures. However, the binding interface is more extensive in Syp. CONCLUSIONS: Most SH2 targets have hydrophobic residues at the third position following the phosphotyrosine, and the Syp structure confirms that the peptide is anchored to the SH2 surface by this residue and by the phosphotyrosine. In addition, the Syp structure has revealed that sequence specificity can extend across the five residues following the phosphotyrosine, and has shown how the SH2 domain's surface topography can be altered with resulting changes in specificity, while conserving the structure of the central core of the domain.
Crystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase.,Lee CH, Kominos D, Jacques S, Margolis B, Schlessinger J, Shoelson SE, Kuriyan J Structure. 1994 May 15;2(5):423-38. PMID:7521735[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang SQ, Yang W, Kontaridis MI, Bivona TG, Wen G, Araki T, Luo J, Thompson JA, Schraven BL, Philips MR, Neel BG. Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Mol Cell. 2004 Feb 13;13(3):341-55. PMID:14967142
- ↑ Seifert RA, van Koppen A, Bowen-Pope DF. PDGF-AB requires PDGF receptor alpha-subunits for high-affinity, but not for low-affinity, binding and signal transduction. J Biol Chem. 1993 Feb 25;268(6):4473-80. PMID:8440729
- ↑ Tallquist MD, French WJ, Soriano P. Additive effects of PDGF receptor beta signaling pathways in vascular smooth muscle cell development. PLoS Biol. 2003 Nov;1(2):E52. Epub 2003 Nov 17. PMID:14624252 doi:http://dx.doi.org/10.1371/journal.pbio.0000052
- ↑ Chiara F, Goumans MJ, Forsberg H, Ahgren A, Rasola A, Aspenstrom P, Wernstedt C, Hellberg C, Heldin CH, Heuchel R. A gain of function mutation in the activation loop of platelet-derived growth factor beta-receptor deregulates its kinase activity. J Biol Chem. 2004 Oct 8;279(41):42516-27. Epub 2004 Jul 28. PMID:15284236 doi:http://dx.doi.org/10.1074/jbc.M406051200
- ↑ Plattner R, Koleske AJ, Kazlauskas A, Pendergast AM. Bidirectional signaling links the Abelson kinases to the platelet-derived growth factor receptor. Mol Cell Biol. 2004 Mar;24(6):2573-83. PMID:14993293
- ↑ Reddi AL, Ying G, Duan L, Chen G, Dimri M, Douillard P, Druker BJ, Naramura M, Band V, Band H. Binding of Cbl to a phospholipase Cgamma1-docking site on platelet-derived growth factor receptor beta provides a dual mechanism of negative regulation. J Biol Chem. 2007 Oct 5;282(40):29336-47. Epub 2007 Jul 9. PMID:17620338 doi:http://dx.doi.org/10.1074/jbc.M701797200
- ↑ Mellgren AM, Smith CL, Olsen GS, Eskiocak B, Zhou B, Kazi MN, Ruiz FR, Pu WT, Tallquist MD. Platelet-derived growth factor receptor beta signaling is required for efficient epicardial cell migration and development of two distinct coronary vascular smooth muscle cell populations. Circ Res. 2008 Dec 5;103(12):1393-401. doi: 10.1161/CIRCRESAHA.108.176768. Epub, 2008 Oct 23. PMID:18948621 doi:http://dx.doi.org/10.1161/CIRCRESAHA.108.176768
- ↑ Wu E, Palmer N, Tian Z, Moseman AP, Galdzicki M, Wang X, Berger B, Zhang H, Kohane IS. Comprehensive dissection of PDGF-PDGFR signaling pathways in PDGFR genetically defined cells. PLoS One. 2008;3(11):e3794. doi: 10.1371/journal.pone.0003794. Epub 2008 Nov 24. PMID:19030102 doi:http://dx.doi.org/10.1371/journal.pone.0003794
- ↑ Zhou L, Takayama Y, Boucher P, Tallquist MD, Herz J. LRP1 regulates architecture of the vascular wall by controlling PDGFRbeta-dependent phosphatidylinositol 3-kinase activation. PLoS One. 2009 Sep 9;4(9):e6922. doi: 10.1371/journal.pone.0006922. PMID:19742316 doi:http://dx.doi.org/10.1371/journal.pone.0006922
- ↑ Olson LE, Soriano P. PDGFRbeta signaling regulates mural cell plasticity and inhibits fat development. Dev Cell. 2011 Jun 14;20(6):815-26. doi: 10.1016/j.devcel.2011.04.019. PMID:21664579 doi:http://dx.doi.org/10.1016/j.devcel.2011.04.019
- ↑ Lee CH, Kominos D, Jacques S, Margolis B, Schlessinger J, Shoelson SE, Kuriyan J. Crystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase. Structure. 1994 May 15;2(5):423-38. PMID:7521735
|
