A HETEROMORPHIC PROTEIN-TYROSINE-PHOSPHATASE, PTP-PHI, IS REGULATED BY CSF-1 IN MACROPHAGES

A novel protein-tyrosine phosphatase, PTP phi, was cloned from a murin e macrophage cDNA library, As a result of alternative splicing, macrop hage PTP phi mRNAs are predicted to encode two membrane-spanning molec ules and a cytosolic enzyme with identical catalytic domains, The memb rane spanning forms differ in the juxtamembrane region, while a start codon downstream of this region is utilized in the translation of the putative cytosolic form. Expression of PTP phi, mRNA is low and restri cted to macrophage cell lines, macrophage-rich tissues, and brain, kid ney, and heart. The mRNA in macrophages and heart is similar to 2.8 ki lobases (kb), However, a similar to 5.5-kb transcript in brain and kid ney indicates a fourth isoform encoding a large extracellular domain. The similar to 5.5-kb PTP phi brain mRNA encodes the mouse homolog of GLEPP1, a recently reported glomerular epithelial protein. The level o f expression of the mRNA encoding the cytosolic form was very low, and only the membrane-spanning proteins (43 and 47 kDa) could be detected in macrophages. Following addition of colony stimulating factor-1 to quiescent BAC1.2F5 macrophages, PTP phi mRNA and protein were down-reg ulated. The restricted expression of the shorter isoforms of PTP phi a nd their regulation by colony stimulating factor-1 in macrophages sugg est that PTP phi may play a role in mononuclear phagocyte survival, pr oliferation, and/or differentiation.