Protein tyrosine phosphatase variants in human hereditary disorders and disease susceptibilities

Abstract

Reversible tyrosine phosphorylation of proteins is a key regulatory mechanism to steer normal development and physiological functioning of multicellular organisms. Phosphotyrosine dephosphorylation is exerted by members of the super-family of protein tyrosine phosphatase (PTP) enzymes and many play such essential roles that a wide variety of hereditary disorders and disease susceptibilities in man are caused by PTP alleles. More than two decades of PTP research has resulted in a collection of PTP genetic variants with corresponding consequences at the molecular, cellular and physiological level. Here we present a comprehensive overview of these PTP gene variants that have been linked to disease states in man. Although the findings have direct bearing for disease diagnostics and for research on disease etiology, more work is necessary to translate this into therapies that alleviate the burden of these hereditary disorders and disease susceptibilities in man.

Keywords: AURKA; Band 4.1/Ezrin/Radixin/Moesin; CAM; CD; CMT; Cell signaling; Charcot–Marie–Tooth; Crohn's disease; DEP-1; DUSP; Density-enhanced phosphatase-1; Disease susceptibility; EYA; FERM; FNIII; GLEPP1; HPE; HTT; IR; Ig; JMML; KIND; MAP kinase phosphatase; MKP; MS; MTMR; NS; Noonan syndrome; PDZ; PHTS; PI(3,4,5)P3; PRL; PSD95/Dlg/ZO-1; PTEN; PTEN hamartoma tumor syndromes; PTP; Phosphotyrosine dephosphorylation; Post-translational modification; RA; RLS; RPTP; RTK; SCID; SFK; SH2; SLE; SNP; STEP; Src homology type 2; Src-family tyrosine kinase; X-linked myotubular myopathy; XLMTM; aurora kinase A; cell adhesion molecule; dual-specificity PTP; eyes absent; fibronectin type III; glomerular epithelial protein 1; hereditary haemorrhagic telangiectasia; holoprosencephaly; immunoglobulin; insulin receptor; juvenile myelomonocytic leukemia; kinase non-catalytic C-lobe domain; multiple sclerosis; myotubularin-related protein; phosphatase and tensin homolog; phosphatase of regenerating liver; phosphatidylinositol 3,4,5-triphosphate; protein tyrosine phosphatase; receptor tyrosine kinase; receptor-type PTP; restless legs syndrome; rheumatoid arthritis; severe combined immunodeficiency; single nucleotide polymorphism; striatal-enriched PTP; systemic lupus erythematosus.