Disease relevance of Ptpn12

• We have used lambda phage analysis to elucidate the complete genomic structure of an intracellular member of this family, the murine MPTP-PEST gene [1].

High impact information on Ptpn12

• Phosphorylation of this site together with the intact phosphotyrosine-binding domain was essential for ShcA binding to the protein-tyrosine phosphatase PTP-PEST [2].
• Overexpression of a PTP-PEST binding-defective mutant of p52(Shc) (S29A) enhanced insulin-induced ERK activation in insulin receptor-overexpressing HIRc-B cells [2].
• TPA-induced ShcA phosphorylation at this site (and hence, its association with PTP-PEST) was inhibited by a protein kinase C-specific inhibitor and was induced by overexpression of constitutively active mutants of protein kinase Calpha, -epsilon, and -delta isoforms [2].
• The cytoplasmic protein tyrosine phosphatase (PTP)-proline-glutamic acid-serine-threonine amino acid sequences (PEST) was also found to be associated with gelsolin in osteoclast podosomes and with stimulation of alpha(v)beta(3)-regulated phosphorylation of PTP-PEST [3].
• Our studies revealed that Csk was associated with PTP-PEST in a variety of cell types, including non-hemopoietic cells [4].

Biological context of Ptpn12

• Defects in embryonic mesenchyme as well as subsequent failure of proper vascularization, liver development and somatogenesis, seemed likely to induce lethality at this stage of development, and these results confirm that PTP-PEST plays an essential function in early embryogenesis [5].
• We observed an increased level of tyrosine phosphorylation of p130cas protein in E9.5 PTP-PEST(-/-) embryos, a first evidence of biochemical defect leading to abnormal growth and development [5].
• Eight overlapping lambda phage clones representing the MPTP-PEST locus were isolated from a 129/sv mouse genomic library [1].
• Finally, fluorescence in situ hybridization with MPTP-PEST genomic DNA refines the map position of MPTP-PEST to mouse chromosome 5A3 to B [1].
• Detailed comparison of the position of intron/exon boundaries of the phosphatase domain of MPTP-PEST to those of several other protein tyrosine phosphatases indicates that the MPTP-PEST catalytic domain contains additional exons as a consequence of the insertion of novel introns [1].

Anatomical context of Ptpn12

• Essential function of PTP-PEST during mouse embryonic vascularization, mesenchyme formation, neurogenesis and early liver development [5].
• Indirect immunofluorescence in COS-1 cells against a heterologous epitope tag attached to the N-terminus of MPTP-PEST, together with cellular fractionation and Western-blot experiments from different murine cell lines, indicate that MPTP-PEST is a free cytosolic protein of 112 kDa [6].
• We conclude that gelsolin plays a key role in recruitment of signaling proteins to the plasma membrane through phospholipid-protein interactions and by regulation of their phosphorylation status through its association with PTP-PEST [3].

Associations of Ptpn12 with chemical compounds

• This interaction involved the SH3 region of p50(csk) and a proline-rich region (PPPLPERTPESFVLADM) outside the catalytic region of PTP-PEST [4].

Other interactions of Ptpn12

• Through its specific association to p130cas and further dephosphorylation, PTP-PEST plays a critical role in cell-matrix interactions, which are essential during embryogenesis [5].
• Insulin also induced ShcA/PTP-PEST association, although to a lesser extent than TPA [2].

Analytical, diagnostic and therapeutic context of Ptpn12

• Reverse transcriptase PCR and Northern-blot analysis show that MPTP-PEST mRNA is expressed throughout murine development [6].
• Moreover, PTP-PEST and PEP were found to accumulate primarily in distinct intracellular compartments in cell fractionation studies [4].

References