PTPRA explained

Receptor-type tyrosine-protein phosphatase alpha is an enzyme that in humans is encoded by the PTPRA gene.^{[1] [2] [3]}

Function

The protein encoded by this gene is a member of the receptor tyrosine phosphatases (RTP), a family of protein tyrosine phosphatases. RTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This RTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type RTP. This RTP has been shown to dephosphorylate and activate Src family tyrosine kinases,^[4] and is implicated in the regulation of integrin signaling, cell adhesion and proliferation. Three alternatively spliced variants of this gene, which encode two distinct isoforms, have been reported.

Interactions

PTPRA has been shown to interact with Grb2^{[5] [6] [7]} and KCNA2.^[8]

Further reading

• Mustelin T, Hunter T . Meeting at mitosis: cell cycle-specific regulation of c-Src by RPTPalpha . Sci. STKE . 2002 . 115 . PE3 . 2002 . 11796915 . 10.1126/stke.2002.115.pe3 . 1111167 .
• Zheng XM, Wang Y, Pallen CJ . Cell transformation and activation of pp60c-src by overexpression of a protein tyrosine phosphatase . Nature . 359 . 6393 . 336–9 . 1992 . 1383828 . 10.1038/359336a0 . 1992Natur.359..336Z . 1283722 .
• Jirik FR, Anderson LL, Duncan AM . The human protein-tyrosine phosphatase PTP alpha/LRP gene (PTPA) is assigned to chromosome 20p13 . Cytogenet. Cell Genet. . 60 . 2 . 117–8 . 1992 . 1611910 . 10.1159/000133317 .
• Rao VV, Löffler C, Sap J, Schlessinger J, Hansmann I . The gene for receptor-linked protein-tyrosine-phosphatase (PTPA) is assigned to human chromosome 20p12-pter by in situ hybridization (ISH and FISH) . Genomics . 13 . 3 . 906–7 . 1992 . 1639427 . 10.1016/0888-7543(92)90186-V .
• Sap J, D'Eustachio P, Givol D, Schlessinger J . Cloning and expression of a widely expressed receptor tyrosine phosphatase . Proc. Natl. Acad. Sci. U.S.A. . 87 . 16 . 6112–6 . 1990 . 2166945 . 54482 . 10.1073/pnas.87.16.6112 . 1990PNAS...87.6112S . free .
• Krueger NX, Streuli M, Saito H . Structural diversity and evolution of human receptor-like protein tyrosine phosphatases . EMBO J. . 9 . 10 . 3241–52 . 1990 . 2170109 . 552056 . 10.1002/j.1460-2075.1990.tb07523.x.
• Ohagi S, Nishi M, Steiner DF . Sequence of a cDNA encoding human LRP (leukocyte common antigen-related peptide) . Nucleic Acids Res. . 18 . 23 . 7159 . 1991 . 2175890 . 332805 . 10.1093/nar/18.23.7159 .
• den Hertog J, Tracy S, Hunter T . Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo . EMBO J. . 13 . 13 . 3020–32 . 1994 . 7518772 . 395191 . 10.1002/j.1460-2075.1994.tb06601.x.
• den Hertog J, Pals CE, Peppelenbosch MP, Tertoolen LG, de Laat SW, Kruijer W . Receptor protein tyrosine phosphatase alpha activates pp60c-src and is involved in neuronal differentiation . EMBO J. . 12 . 10 . 3789–98 . 1993 . 7691597 . 413662 . 10.1002/j.1460-2075.1993.tb06057.x.
• Stover DR, Furet P, Lydon NB . Modulation of the SH2 binding specificity and kinase activity of Src by tyrosine phosphorylation within its SH2 domain . J. Biol. Chem. . 271 . 21 . 12481–7 . 1996 . 8647855 . 10.1074/jbc.271.21.12481 . free .
• den Hertog J, Hunter T . Tight association of GRB2 with receptor protein-tyrosine phosphatase alpha is mediated by the SH2 and C-terminal SH3 domains . EMBO J. . 15 . 12 . 3016–27 . 1996 . 8670803 . 450243 . 10.1002/j.1460-2075.1996.tb00665.x.
• Shimizu Y, Sugiyama H, Fujii Y, Sasaki K, Inoue K, Ogawa H, Tamaki H, Miyake S, Oji Y, Soma T, Yamagami T, Hirata M, Ikeda K, Monden T, Kishimoto T . Lineage- and differentiation stage-specific expression of LSM-1 (LPAP), a possible substrate for CD45, in human hematopoietic cells . Am. J. Hematol. . 54 . 1 . 1–11 . 1997 . 8980254 . 10.1002/(SICI)1096-8652(199701)54:1<1::AID-AJH1>3.0.CO;2-1 . 36581335 .
• Lim KL, Lai DS, Kalousek MB, Wang Y, Pallen CJ . Kinetic analysis of two closely related receptor-like protein-tyrosine-phosphatases, PTP alpha and PTP epsilon . Eur. J. Biochem. . 245 . 3 . 693–700 . 1997 . 9183007 . 10.1111/j.1432-1033.1997.00693.x . free .
• Somani AK, Bignon JS, Mills GB, Siminovitch KA, Branch DR . Src kinase activity is regulated by the SHP-1 protein-tyrosine phosphatase . J. Biol. Chem. . 272 . 34 . 21113–9 . 1997 . 9261115 . 10.1074/jbc.272.34.21113 . free .
• Feito MJ, Bragardo M, Buonfiglio D, Bonissoni S, Bottarel F, Malavasi F, Dianzani U . gp 120s derived from four syncytium-inducing HIV-1 strains induce different patterns of CD4 association with lymphocyte surface molecules . Int. Immunol. . 9 . 8 . 1141–7 . 1997 . 9263011 . 10.1093/intimm/9.8.1141 . free .
• Norris K, Norris F, Kono DH, Vestergaard H, Pedersen O, Theofilopoulos AN, Møller NP . Expression of protein-tyrosine phosphatases in the major insulin target tissues . FEBS Lett. . 415 . 3 . 243–8 . 1997 . 9357975 . 10.1016/S0014-5793(97)01133-2 . 9414519 . 1997FEBSL.415..243N .
• Bhandari V, Lim KL, Pallen CJ . Physical and functional interactions between receptor-like protein-tyrosine phosphatase alpha and p59fyn . J. Biol. Chem. . 273 . 15 . 8691–8 . 1998 . 9535845 . 10.1074/jbc.273.15.8691 . free .
• Harder KW, Moller NP, Peacock JW, Jirik FR . Protein-tyrosine phosphatase alpha regulates Src family kinases and alters cell-substratum adhesion . J. Biol. Chem. . 273 . 48 . 31890–900 . 1998 . 9822658 . 10.1074/jbc.273.48.31890 . free .

Notes and References

1. Jirik FR, Janzen NM, Melhado IG, Harder KW . Cloning and chromosomal assignment of a widely expressed human receptor-like protein-tyrosine phosphatase . FEBS Lett . 273 . 1–2 . 239–42 . December 1990 . 2172030 . 10.1016/0014-5793(90)81094-5 . 31501542 . free . 1990FEBSL.273..239J .
2. Kaplan R, Morse B, Huebner K, Croce C, Howk R, Ravera M, Ricca G, Jaye M, Schlessinger J . Cloning of three human tyrosine phosphatases reveals a multigene family of receptor-linked protein-tyrosine-phosphatases expressed in brain . Proc Natl Acad Sci U S A . 87 . 18 . 7000–4 . October 1990 . 2169617 . 54670 . 10.1073/pnas.87.18.7000 . 1990PNAS...87.7000K . free .
3. Web site: Entrez Gene: PTPRA protein tyrosine phosphatase, receptor type, A.
4. den Hertog J, Pals CE, Peppelenbosch MP, Tertoolen LG, de Laat SW, Kruijer W . Receptor protein tyrosine phosphatase alpha activates pp60c-src and is involved in neuronal differentiation. EMBO Journal. 1993. 12. 10. 3789–98 . 10.1002/j.1460-2075.1993.tb06057.x. 7691597. 413662. free.
5. den Hertog J, Hunter T . Tight association of GRB2 with receptor protein-tyrosine phosphatase alpha is mediated by the SH2 and C-terminal SH3 domains . EMBO J. . 15 . 12 . 3016–27 . June 1996 . 8670803 . 450243 . 10.1002/j.1460-2075.1996.tb00665.x.
6. den Hertog J, Tracy S, Hunter T . Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo . EMBO J. . 13 . 13 . 3020–32 . July 1994 . 7518772 . 395191 . 10.1002/j.1460-2075.1994.tb06601.x.
7. Zheng XM, Resnick RJ, Shalloway D . Mitotic activation of protein-tyrosine phosphatase alpha and regulation of its Src-mediated transforming activity by its sites of protein kinase C phosphorylation . J. Biol. Chem. . 277 . 24 . 21922–9 . June 2002 . 11923305 . 10.1074/jbc.M201394200 . 5641391 . free .
8. Tsai W, Morielli AD, Cachero TG, Peralta EG . Receptor protein tyrosine phosphatase alpha participates in the m1 muscarinic acetylcholine receptor-dependent regulation of Kv1.2 channel activity . EMBO J. . 18 . 1 . 109–18 . January 1999 . 9878055 . 1171107 . 10.1093/emboj/18.1.109 .