Tyrosine phosphorylation of a 120,000 dalton membrane-associated protein by the neural form of pp60c-src, pp60c-src+

The c-src proto-oncogene encodes a 60,000 dalton tyrosine kinase, pp60c-src, which is the prototype member of the family of non-receptor tyrosine kinases. A neural-specific form of pp60c-src, pp60c-src+, is detected only in neurons of the central nervous system. pp60c-src+ contains a six amino acid insert (neural insert) in the SH3 region that is generated by alternative splicing. Previous reports indicate that the profiles of proteins phosphorylated on tyrosine in chick embryo fibroblast (CEF) cells by pp60c-src+ or pp60c-src are equivalent. In this report, the activities of pp60c-src+ and pp60c-src, as well as the activated variants, pp60(527F+) and pp60(527F), were compared in CEF cells by examining the steady-state levels of tyrosine phosphorylation of several known pp60src substrates. Most substrates examined were phosphorylated on tyrosine to equivalent levels in CEF cells expressing either the neural- or fibroblast-specific src gene products. However, the relative extent of tyrosine phosphorylation of a 120 kDa protein (p120) was increased in cells expressing the neuronal forms of either c-src or c-src527F. The increased tyrosine phosphorylation of p120 did not appear to be caused by the neural insert facilitating a specific interaction between pp60c-src+ and p120. These data indicate that preferential phosphorylation of p120 in neural cells may contribute to the specialized function of pp60c-src+ in neural cells.