IDENTIFICATION OF A HORMONALLY REGULATED PROTEIN-TYROSINE-PHOSPHATASEASSOCIATED WITH BONE AND TESTICULAR-DIFFERENTIATION

Absence of the tyrosine kinase activity of c-src and c-fms results in impairment of bone remodeling. Such dysfunction underscores the import ance of tyrosine phosphorylation, yet the role of protein tyrosine pho sphatases in bone metabolism remains unexamined. We have isolated the cDNA for a novel receptor-like tyrosine phosphatase expressed in bone and testis named osteotesticular protein tyrosine phosphatase (OST-PTP ). The deduced 1711-residue protein possesses an extracellular domain with 10 fibronectin type III repeats and a cytoplasmic region with two catalytic domains. In primary rat osteoblasts, the 5.8-kilobase OST-P TP transcript is up-regulated in differentiating cultures and down-reg ulated in late stage mineralizing cultures. In addition, a presumed al ternate transcript of 4.8-5.0 kilobases, which may lack PTP domains, i s present in pro liferating osteoblasts, but not detectable at other s tages. Parathyroid hormone, a modulator of bone function, as well as c yclic AMP analogues, increase OST-PTP mRNA 5-8-fold in UMR 106 cells. In situ hybridization of adult rat testis revealed stage-specific expr ession of OST-PTP. OST-PTP may function in signaling pathways during b one remodeling, as well as serve a broader role in cell interactions a ssociated with differentiation in bone and testis.