Fm. Longo et al., LEUKOCYTE COMMON ANTIGEN-RELATED RECEPTOR-LINKED TYROSINE PHOSPHATASE- REGULATION OF MESSENGER-RNA EXPRESSION, The Journal of biological chemistry, 268(35), 1993, pp. 26503-26511
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.