Characterization of the altered form of the c-src gene product in neuronal cells.

The pp60c-src protein that is expressed at high levels in cultures of neurons from rat embryos displays an altered mobility on SDS-polyacrylamide gels due to a structural difference in the amino-terminal region of the molecule. In this report we show that the expression of this unique form of pp60c-src, designated pp60c-src(+), is not restricted to cultured neuronal cells since the pp60c-src molecules expressed in tissues from avian and rat neural tissues also display a retarded electrophoretic mobility. The amino-terminal region from pp60c-src(+) was found to contain a novel phosphorylated tryptic peptide that contains phosphoserine. However, this phosphorylation does not appear to be responsible for the retarded electrophoretic mobility of pp60c-src(+), since the mobility of this protein is not altered by phosphatase treatment under conditions that remove greater than 95% of the radiolabeled phosphate on pp60c-src(+). The altered electrophoretic form of pp60c-src was also shown to be radiolabeled with [3H]myristate, indicating that pp60c-src is fatty-acylated in neurons, as is pp60c-src in fibroblasts. The pp60c-src molecules synthesized in vitro using rabbit reticulocyte lysates programmed with mRNA from embryonic brain migrated more slowly on SDS-polyacrylamide gels than the pp60c-src protein that was translated in vitro using RNA from embryonic limb tissue. These results suggest the possibility that the c-src mRNA expressed in neurons may undergo a unique form of processing to generate the structurally distinct form of neuronal pp60c-src(+).