LEUKOCYTE COMMON ANTIGEN-RELATED RECEPTOR-LINKED TYROSINE PHOSPHATASE- REGULATION OF MESSENGER-RNA EXPRESSION

Receptor-linked tyrosine phosphatases regulate cell growth by dephosph orylating proteins involved in tyrosine kinase signal transduction. Wi thin this gene family, the leukocyte common antigen-related (LAR) gene is of particular interest with respect to the nervous system because it has sequence similarity to the neural cell adhesion molecule N-CAM and is located in a chromosomal region (1p32-33) frequently deleted in neuroectodermal tumors. However, immunostaining has detected LAR in n on-neural tissues, but not in the central nervous system, peripheral n eurons, or adrenal medulla. In this study, rat brain cDNA library LAR clones corresponding to cytoplasmic and 3'-untranslated regions of hum an LAR were identified. Using probes derived from these clones, high s tringency Northern blots revealed approximately 8 kilobase and variabl e length tissue- and cell-specific LAR transcripts in cortex, brainste m, cerebellum, spinal cord, peripheral tissues, and cultured neural, g lial, and pheochromocytoma cells. In situ hybridization showed express ion by brain and dorsal root ganglion neurons. LAR expression was deve lopmentally regulated in a region-dependent manner. Changes in LAR exp ression were also found during nerve growth factor-induced PC12 pheoch romocytoma cell differentiation and with contact-mediated inhibition o f fibroblast growth. These observations and studies demonstrating neur otrophins functioning via tyrosine kinase receptors suggest that LAR r epresents an additional mechanism regulating neural development.