Protein tyrosine phosphatase
|PDB structures||RCSB PDB PDBe PDBsum|
Protein tyrosine phosphatases are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. Protein tyrosine (pTyr) phosphorylation is a common post-translational modification that can create novel recognition motifs for protein interactions and cellular localization, affect protein stability, and regulate enzyme activity. As a consequence, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase; EC 188.8.131.52) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation.
Together with tyrosine kinases, PTPs regulate the phosphorylation state of many important signalling molecules, such as the MAP kinase family. PTPs are increasingly viewed as integral components of signal transduction cascades, despite less study and understanding compared to tyrosine kinases.
PTPs have been implicated in regulation of many cellular processes, including, but not limited to:
Links to all 107 members of the protein tyrosine phosphatase family can be found in the template at the bottom of this article.
The class I PTPs, are the largest group of PTPs with 99 members, which can be further subdivided into
- 38 classical PTPs
- 21 receptor tyrosine phosphatase
- 17 nonreceptor-type PTPs
- 61 VH-1-like or dual-specific phosphatases (DSPs)
Dual-specificity phosphatases (dTyr and dSer/dThr) dual-specificity protein-tyrosine phosphatases. Ser/Thr and Tyr dual-specificity phosphatases are a group of enzymes with both Ser/Thr (EC 184.108.40.206) and tyrosine-specific protein phosphatase (EC 220.127.116.11) activity able to remove the serine/threonine or the tyrosine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes that have been phosphorylated under the action of a kinase. Dual-specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle.
The class II PTPs contain only one member, low-molecular-weight phosphotyrosine phosphatase (LMPTP).
Cdc25 phosphatases (dTyr and/or dThr)
The class IV PTPs contains four members, Eya1-4.
This class is believed to have evolved separately from the other three.
Based on their cellular localization, PTPases are also classified as:
- Receptor-like, which are transmembrane receptors that contain PTPase domains. In terms of structure, all known receptor PTPases are made up of a variable-length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains, or carbonic anhydrase-like domains in their extracellular region. In general, the cytoplasmic region contains two copies of the PTPase domain. The first seems to have enzymatic activity, whereas the second is inactive.
- Non-receptor (intracellular) PTPases
All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and possess a similar core structure made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha-loop that encompasses the PTP signature motif. Functional diversity between PTPases is endowed by regulatory domains and subunits.
Individual PTPs may be expressed by all cell types, or their expression may be strictly tissue-specific. Most cells express 30% to 60% of all the PTPs, however hematopoietic and neuronal cells express a higher number of PTPs in comparison to other cell types. T cells and B cells of hematopoietic origin express around 60 to 70 different PTPs. The expression of several PTPS is restricted to hematopoietic cells, for example, LYP, SHP1, CD45, and HePTP.
- Dixon JE, Denu JM (1998). "Protein tyrosine phosphatases: mechanisms of catalysis and regulation". Curr Opin Chem Biol 2 (5): –. PMID 9818190.
- Paul S, Lombroso PJ (2003). "Receptor and nonreceptor protein tyrosine phosphatases in the nervous system". Cell. Mol. Life Sci. 60 (11): –. doi:10.1007/s00018-003-3123-7. PMID 14625689.
- Sun JP, Zhang ZY, Wang WQ (2003). "An overview of the protein tyrosine phosphatase superfamily". Curr Top Med Chem 3 (7): –. PMID 12678841.
- Alonso A, Sasin J, et al. (2004). "Protein tyrosine phosphatases in the human genome". Cell 117 (6): 699–711. doi:10.1016/j.cell.2004.05.018. PMID 15186772.
- Wo YY, Shabanowitz J, Hunt DF, Davis JP, Mitchell GL, Van Etten RL, McCormack AL (1992). "Sequencing, cloning, and expression of human red cell-type acid phosphatase, a cytoplasmic phosphotyrosyl protein phosphatase". J. Biol. Chem. 267 (15): 10856–10865. PMID 1587862.
- Shekels LL, Smith AJ, Bernlohr DA, Van Etten RL (1992). "Identification of the adipocyte acid phosphatase as a PAO-sensitive tyrosyl phosphatase". Protein Sci. 1 (6): 710–721. doi:10.1002/pro.5560010603. PMC 2142247. PMID 1304913.
- William C. Plaxton; Michael T. McManus (2006). Control of primary metabolism in plants. Wiley-Blackwell. pp. 130–. ISBN 978-1-4051-3096-7. Retrieved 12 December 2010.
- Knapp S, Longman E, Debreczeni JE, Eswaran J, Barr AJ (2006). "The crystal structure of human receptor protein tyrosine phosphatase kappa phosphatase domain 1". Protein Sci. 15 (6): –. doi:10.1110/ps.062128706. PMC 2242534. PMID 16672235.
- Perrimon N, Johnson MR, Perkins LA, Melnick MB (1996). "The nonreceptor protein tyrosine phosphatase corkscrew functions in multiple receptor tyrosine kinase pathways in Drosophila". Dev. Biol. 180 (1): –. doi:10.1006/dbio.1996.0285. PMID 8948575.
- Barford D, Das AK, Egloff MP (1998). "The structure and mechanism of protein phosphatase s: insights into catalysis and regulation". Annu. Rev. Biophys. Biomol. Struct. 27 (1): –. doi:10.1146/annurev.biophys.27.1.133. PMID 9646865.
- Su XD, Taddei N, Stefani M, Ramponi G, Nordlund P (August 1994). "The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase". Nature 370 (6490): 575–8. doi:10.1038/370575a0. PMID 8052313.
- Stuckey JA, Schubert HL, Fauman EB, Zhang ZY, Dixon JE, Saper MA (August 1994). "Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 A and the complex with tungstate". Nature 370 (6490): 571–5. doi:10.1038/370571a0. PMID 8052312.
- Yuvaniyama J, Denu JM, Dixon JE, Saper MA (May 1996). "Crystal structure of the dual specificity protein phosphatase VHR". Science 272 (5266): 1328–31. doi:10.1126/science.272.5266.1328. PMID 8650541.
- Aceti DJ, Bitto E, Yakunin AF, et al. (October 2008). "Structural and functional characterization of a novel phosphatase from the Arabidopsis thaliana gene locus At1g05000". Proteins 73 (1): 241–53. doi:10.1002/prot.22041. PMID 18433060.
- Mustelin T, Vang T and Bottini N. (2005). "Protein tyrosine phosphatases and the immune response". Nat. Rev. Immunol. 5 (1): 43–57. doi:10.1038/nri1530. PMID 15630428.
- PTP Summary and Relevant Publications at Monash University
- Protein-Tyrosine-Phosphatase at the US National Library of Medicine Medical Subject Headings (MeSH)
- EC 18.104.22.168