CLONING, EXPRESSION AND CHROMOSOMAL LOCALIZATION OF A NEW PUTATIVE RECEPTOR-LIKE PROTEIN TYROSINE PHOSPHATASE

We have isolated a mouse cDNA of 5.7 kb, encoding a new member of the family of receptor-like protein tyrosine phosphatases, termed mRPTP-mu. The cDNA predicts a protein of 1432 amino acids (not including signal peptide) with a calculated M(r) of 161 636. In addition, we have cloned the human homologue, hRPTP-mu, which shows 98.7% amino acid identity to mRPTP-mu. The predicted mRPTP-mu protein consists of a 722 amino acid extracellular region, containing 13 potential N-glycosylation sites, a single transmembrane domain and a 688 amino acid intracellular part containing 2 tandem repeats homologous to the catalytic domains of other tyrosine phosphatases. The N-terminal extracellular part contains a region of about 170 amino acids with no sequence similarities to known proteins, followed by one Ig-like domain and 4 fibronectin type III-like domains. The intracellular part is unique in that the region between the transmembrane domain and the first catalytic domain is about twice as large as in other receptor-like protein tyrosine phosphatases. RNA blot analysis reveals a single transcript, that is most abundant in lung and present in much lower amounts in brain and heart. Transfection of the mRPTP-mu cDNA into COS cells results in the synthesis of a protein with an apparent M(r) of 195 000, as detected in immunoblots using an antipeptide antibody. The human RPTP-mu gene is localized on chromosome 18pter-q11, a region with frequent abnormalities implicated in human cancer.