Phosphatase Family LMWPTP

Phosphatase Classification: Superfamily Cys-based III: Family LMWPTP

Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) is a small protein (LMW) which dephosphorylates proteins on phospho-tyrosine.

Evolution

LMWPTP is present in most eukaryotes, though lost from from alveolates, trypanosoma, leishmania. It is also found in many bacteria and archaea.

Domain Structure

Most eukaryotic LMWPTP consist almost entirely of a phosphatase domain.

Function

In eukaryotes, LMWPTP dephosphorylates many receptor tyrosine kinases, such PDGFR, InsR, and Eph [1]. It is a substrate for Src and Src phosphorylation creates a Grb2 SH2 domain-binding site. Accordingly it has been implicated in cancer progression [2]. Polymorphisms have also been implicated in metabolic and immune diseases.

Human LMWPTP is also known to be a declycating agent, removing ribulose 5-phosphate from proteins [3, 4], in collaboration with Fructosamine Kinase.

Yeast lacks classical TKs but the least homolog (LTP1) is a tyrosine-specific phosphatase and may dephosphorylate the immunophilin Fpr3 in vivo [5], on a residue likely phosphorylated by CK2 [6].

In prokaryotes, the molecular function is not fully understood. It is involved in the syntheisis and translocation of exopolysaccharides (EPS) and capsular polysaccharides (CPS) in E. coli. YwlE also acts as an arginine phosphatase [7]. In many species, the LMWPTP is chromosomally adjacent to a fructosamine kinase, suggesting that it's major role is in protein deglycation [8]. E. coli Wzb is known to dephosphorylate the atypical tyrosine kinase Wzc [9].

Reference

1. Kikawa KD, Vidale DR, Van Etten RL, and Kinch MS. Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation. J Biol Chem. 2002 Oct 18;277(42):39274-9. DOI:10.1074/jbc.M207127200 |
2. Alho I, Costa L, Bicho M, and Coelho C. The role of low-molecular-weight protein tyrosine phosphatase (LMW-PTP ACP1) in oncogenesis. Tumour Biol. 2013 Aug;34(4):1979-89. DOI:10.1007/s13277-013-0784-1 |
4. Van Schaftingen E, Collard F, Wiame E, and Veiga-da-Cunha M. Enzymatic repair of Amadori products. Amino Acids. 2012 Apr;42(4):1143-50. DOI:10.1007/s00726-010-0780-3 |
5. Magherini F, Gamberi T, Paoli P, Marchetta M, Biagini M, Raugei G, Camici G, Ramponi G, and Modesti A. The in vivo tyrosine phosphorylation level of yeast immunophilin Fpr3 is influenced by the LMW-PTP Ltp1. Biochem Biophys Res Commun. 2004 Aug 20;321(2):424-31. DOI:10.1016/j.bbrc.2004.06.158 |
6. Wilson LK, Dhillon N, Thorner J, and Martin GS. Casein kinase II catalyzes tyrosine phosphorylation of the yeast nucleolar immunophilin Fpr3. J Biol Chem. 1997 May 16;272(20):12961-7. DOI:10.1074/jbc.272.20.12961 |
7. Fuhrmann J, Subramanian V, and Thompson PR. Targeting the arginine phosphatase YwlE with a catalytic redox-based inhibitor. ACS Chem Biol. 2013 Sep 20;8(9):2024-32. DOI:10.1021/cb4001469 |
8. Gemayel R, Fortpied J, Rzem R, Vertommen D, Veiga-da-Cunha M, and Van Schaftingen E. Many fructosamine 3-kinase homologues in bacteria are ribulosamine/erythrulosamine 3-kinases potentially involved in protein deglycation. FEBS J. 2007 Sep;274(17):4360-74. DOI:10.1111/j.1742-4658.2007.05948.x |
9. Temel DB, Dutta K, Alphonse S, Nourikyan J, Grangeasse C, and Ghose R. Regulatory interactions between a bacterial tyrosine kinase and its cognate phosphatase. J Biol Chem. 2013 May 24;288(21):15212-28. DOI:10.1074/jbc.M113.457804 |
10. Fortpied J, Gemayel R, Vertommen D, and Van Schaftingen E. Identification of protein-ribulosamine-5-phosphatase as human low-molecular-mass protein tyrosine phosphatase-A. Biochem J. 2007 Aug 15;406(1):139-45. DOI:10.1042/BJ20061485 |