Antibody-induced dimerization of HARPTPα-EGFR chimera suggests a ligand dependent mechanism of regulation for RPTPα

We developed a system to study the function of the ectodomain of RPTP alpha, a transmembrane protein-tyrosine phosphatase, by fusing the HA-epitope tagged ectodomain of RPTP alpha to the transmembrane and intracellular domain of the epidermal growth factor receptor, EGFR, a receptor protein-tyrosine kinase that is activated by dimerization, Although the use of chemical crosslinkers shows that preformed HARPTP alpha -EGFR dimers exist, bivalent anti-HA-tag antibody activated HARPTP alpha -EGFR chimeras, suggesting this system may be used to study regulation of dimerization. We used this system to show that newborn calf serum may contain (a) potential ligand(s) for RPTPa. Our results suggest that RPTPa dimerization and thus activity may be affected by ligand binding. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B,V, All rights reserved.