LIPRINS, A FAMILY OF LAR TRANSMEMBRANE PROTEIN-TYROSINE PHOSPHATASE-INTERACTING PROTEINS

LAR family transmembrane protein-tyrosine phosphatases function in axo n guidance and mammary gland development. In cultured cells, LAR binds to the intracellular, coiled coil LAB-interacting protein at discrete ends of focal adhesions, implicating these proteins in the regulation of cell-matrix interactions. We describe seven LAB-interacting protei n-like genes in humans and Caenorhabditis elegans that form the liprin gene family, Based on sequence similarities and binding characteristi cs, liprins are subdivided into alpha-type and beta-type liprins. The C-terminal, non-coiled coil regions of alpha-liprins bind to the membr ane-distal phosphatase domains of LAR family members, as well as to th e C-terminal, non-coiled coil region of beta-liprins. Both alpha- and beta-liprins homodimerize via their N-terminal, coiled coil regions. L iprins are thus multivalent proteins that potentially form complex str uctures. Some liprins have broad mRNA tissue distributions, whereas ot hers are predominately expressed in the brain. Go-expression studies i ndicate that liprin-alpha 2 alters LAR cellular localization and induc es LAR clustering. We propose that liprins function to localize LAR fa mily tyrosine phosphatases at specific sites on the plasma membrane, p ossibly regulating their interaction with the extracellular environmen t and their association with substrates.