Protein tyrosine Phosphatase Shp

Kim CH, Qu CK, Hangoc G, et al. Abnormal chemokine-induced responses of immature and mature hematopoietic cells from motheaten mice implicate the protein tyrosine phosphatase SHP-1 in chemokine responses. J Exp Med 1999 190(5) 681-690. 

Sattler, M., Salgja, R., Shrikhande, G., Verma, S., Choi, J.L., Rohrschneider, L.R., and Griffin, J.D., 1997, The phosphatidyhnositol polyphosphate 5-phosphatase SHIP and the protein tyrosine phosphatase SHP-2 form a complex in hematopoietic cells which can be regulated by BCR/ABL and growth factors. Oncogene, 15 2379-2384. 

The insulin receptor substrate IRS couples the insulin receptor to sequential effector molecules (review Ogawa et al., 1998). On binding of insulin to the insulin receptor, the tyrosine kinase activity of the receptor is stimulated. The IRS protein is phosphory-lated at several Tyr residues, which then serve as attachment points for sequential effector molecules as e.g. the Grb2-mSos complex, the P13-kinase and the protein tyrosine phosphatase SHP-2. The IRS protein also has a phosphotyrosine binding domain and a PH domain. Both modules are required for signal transduction in vivo. It is assumed that the PTB domain binds to autophosphorylation sites of the insulin receptor and that the PH domain is involved in membrane association of IRS. 

Another AT2 pathway linked to apoptosis leads to a stimulation of a soluble protein tyrosine phosphatase, SHP-1, an enzyme that associates with insulin receptor substrate (IRS)-2 (Cui et al. 2002). Overexpression of a dominant negative form of SHP-1 in PC12W cells has been found to attenuate AT2 receptor-mediated inhibition of insulin signaling. Since insulin activates Akt, it is interesting that the mechanism of apoptosis in the angiotensin II-treated PC12W cell involves the dephosphorylation and inactivation of Akt. In NIE-115 neuroblastoma cells,... 

Site-specific incorporation of a nonhydrolyzable phosphotyrosine analog revealed a role for phosphorylation of protein tyrosine phosphatase SHP-2 in cell signaling (59). The phosphorylated SHP-2 protein showed improved activity in catalyzing phosphate release than its nonphosphorylated counterpart. 

Yang J, Cheng Z, Niu T et al (2000) Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1. J Biol Chem 275 4066 071... 

Liu X, Qu CK (2011) Protein tyrosine phosphatase SHP-2 (PTPNll) in hematopoiesis and leukemogenesis. J Signal Transduct 2011 195-239... 

Mutations in PTPNll, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 29 465-468... 

Barford D, Neel BG (1998) Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2. Structure 6 249-254... 

Matozaki T, Murata Y, Saito Y et al (2009) Protein tyrosine phosphatase SHP-2 a proto-... 

Fig. 7.2-6 Domain architecture of protein tyrosine phosphatases SHP-1 and SHP-2. The highlighted tyrosine residues are modified by protein tyrosine kinases.

Jiao H, Berrada K, Yang W, Tabrizi M, Platanias LC, Yi T Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1. Mol Cell Biol 1996 16 6985-6992. 

Blery M, Kubagawa H, Chen CC, Vely F, Cooper MD, Vivier E (1998) The paired Ig-like receptor PIR-B is an inhibitory receptor that recruits the protein-tyrosine phosphatase SHP-1. Proc Natl Acad Sci USA 95 2446-2451... 

Greer, S. F. Justement, L. B., CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1. J Immunol 1999, 162, (9), 5278-86. 

SHP binds to She (Sre Pomology and collagen) adaptor protein and to SHP-2 protein tyrosine phosphatase via SHIP S SH2 domain (Liu et al.,... 

Abbreviations c-Abl, Abelson protein tyrosine kinase c-Crk-II, CTIO regulator of kinase Csk, C-terminal Src kinase GFP, green fluorescent protein Hpal, restriction endonuclease from Haemophilus parainfluenzae MBP, maltose-binding protein SHP-2, Src homology 2 protein tyrosine phosphatase Src, Rous sarcoma vims kinase. 

Eurther, a compound collection based on the scaffold of the natural product Euranodictin (Eigure 9.12D) revealed a previously uncharacterized inhibitor class for the protein tyrosine phosphatases PTPIB and Shp-2." A compound collection which embodies the underlying scaffold structure of alkaloid cytisine and related natural products (Figure 9.12E) revealed the first inhibitor class of the vascular endothelial protein tyrosine phosphatase (VEPTP) at a hit rate of 1.57% as well as a completely new class of inhibitors for protein tyrosine phosphatase-IB and the phosphatase Shp-2. These two enzymes are targets for the treatment of the metabolic syndrome and diabetes as well as cancer respectively. In these cases the hit rates were ca. 0.3 to 0.4%. The screens revealed selective inhibitors for the proteins." ... 

Bedecs, K., Elbaz, N., Sutren, M., Masson, M., Susini, C., Strosberg, A.D., and Nahmias, C. 1997. Angiotensin II type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase. Biochem. J. 325 449-454. 

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