STRUCTURAL DIVERSITY AND EVOLUTION OF HUMAN RECEPTOR-LIKE PROTEIN TYROSINE PHOSPHATASES

Protein tyrosine phosphatase (PTPases), together with protein tyrosine kinases, regulate the tyrosine phosphorylation that controls cell activities and proliferation. Previously, it has been recognized that both cytosolic PTPases and membrane associated, receptor-like PTPases exist. In order to examine the structural diversity of receptor-like PTPases, we isolated human cDNA clones that cross-hybridized to a Drosophila PTPase cDNA clone, DPTP12, under non-stringent hybridization conditions. The cDNA clones thus isolated included LCA and six other novel receptor-like PTPases, named HPTPα, β, γ, δ, ε and ζ. The cytoplasmic regions of HPTPα and ε are highly homologous, and are composed of two tandemly duplicated PTPase-like domains. The extracellular regions of HPTPα and ε are, respectively, 123 amino acids and 27 amino acids, and do not have obvious similarity to any known protein. The cytoplasmic region of HPTPβ contains only one PTPase domain. The extracellular region of HPTPβ, which is 1599 amino acids, is composed of 16 fibronectin type-III repeats. HPTPδ is very similar to leukocyte common antigen related molecule (LAR), in both the extracellular and cytoplasmic regions. Partial sequences of HPTPγ and ζ indicate that they are highly homologous and contain two PTPase-like domains. The PTPase-like domains of HPTPα, β and δ expressed in Escherichia coli had tyrosine phosphatase activities.