EXPRESSION OF A NOVEL FORM OF THE P561CK PROTOONCOGENE IN RAT CEREBELLAR GRANULAR NEURONS

The src family protein tyrosine kinases (PTKs) are nonreceptor kinases . Some PTKs of this family are ubiquitously expressed, whereas others have a more restricted expression, as in neurons. Lymphoid cell kinase (lck) p56lck is highly expressed in tissues of lymphoid origin and be lieved to be specific for hematopoietic cells. Reports suggesting that CD4 is expressed in neurons prompted us to analyze the possibility th at p56lck is also expressed in these cells. By western blot and immuno precipitations using anti-lck antibody, an lck-like protein was detect ed in lysates from primary cultures of rat cerebellar granular neurons . This 56-kDa phosphoprotein was autophosphorylated in vitro and also phosphorylated enolase, similarly to p56lck. It was shown to be locate d actually in the neurons by immunocytofluorescence. Partial proteolys is mapping showed that the 56-kDa phosphoprotein had a peptide pattern very similar to the p56lck protein. Retrotranscription-PCR allowed th e detection of an lck RNA in the neurons. The lck kinase domain was co mpletely identical to the lymphocyte lck kinase domain, but the 5' end was modified in the neurons. These results show that p56lck is not ly mphoid specific as is widely believed; its expression in neurons might underlie the toxicity of the HIV glycoprotein gp120 to neurons.