Leukocyte common antigen-related receptor-linked tyrosine phosphatase: Regulation of mRNA expression

Receptor-linked tyrosine phosphatases regulate cell growth by dephosphorylating proteins involved in tyrosine kinase signal transduction. Within 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 non-neural tissues, but not in the central nervous system, peripheral neurons, or adrenal medulla. In this study, rat brain cDNA library LAR clones corresponding to cytoplasmic and 3′-untranslated regions of human LAR were identified. Using probes derived from these clones, high stringency Northern blots revealed ∼8 kilobase and variable length tissue- and cell-specific LAR transcripts in cortex, brainstem, cerebellum, spinal cord, peripheral tissues, and cultured neural, glial, and pheochromocytoma cells. In situ hybridization showed expression by brain and dorsal root ganglion neurons. LAR expression was developmentally regulated in a region-dependent manner. Changes in LAR expression were also found during nerve growth factor-induced PC 12 pheochromocytoma cell differentiation and with contactmediated inhibition of fibroblast growth. These observations and studies demonstrating neurotrophins functioning via tyrosine kinase receptors suggest that LAR represents an additional mechanism regulating neural development.