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PDGF receptor as a specific in vivo target for low M r phosphotyrosine protein phosphatase
Author(s) -
Chiarugi Paola,
Cirri Paolo,
Raugei Giocanni,
Camici Guido,
Dolfi Fabrizio,
Berti Andrea,
Ramponi Giampietro
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00947-8
Subject(s) - phosphatase , mutant , phosphorylation , mutagenesis , microbiology and biotechnology , receptor , site directed mutagenesis , protein phosphatase 2 , biochemistry , biology , protein tyrosine phosphatase , dusp6 , chemistry , gene
Low M r phosphotyrosine protein phosphatase (LMWPTP) is a 18 kDa cytosolic enzyme widely distributed in eukaryotic cells. LMW‐PTP catalyses the hydrolysis of phosphotyrosine residues and overexpression of the enzyme in normal and transformed cells inhibits cell proliferation. Site directed mutagenesis, together with crystallographic studies, have contributed to clarify the catalytic mechanism, which involves the active site signature sequence C 12 R 18 , a main feature of all PTPase family members. In order to identify the LMW‐PTP substratels we have expressed in NIH‐3T3 cells a catalytically inert Cys 12 to Ser phosphatase mutant which has preserved its capacity for substrate binding. Overexpression of the mutant phosphatase leads to enhanced cell proliferation and serum induced mitogenesis, indicating that the mutation results in the production of a dominant negative protein. Analysis of mutant LMW‐PTP expressing cells has enabled us to demonstrate an association between LMW‐PTP and platelet derived growth factor receptor that appears to be highly specific. Our data suggest a catalytic action of LMW‐PTP on the phosphorylated platelet derived growth factor receptor.