Tyrosine phosphorylation of membrane-associated tubulin in nerve growth cones enriched in pp60c-src

The product of the c-src proto-oncogene (pp60c-src) is a tyrosine-specific protein kinase that is expressed in two phases of neural development. In post-mitotic neuronal cells undergoing terminal differentiation, pp60c-src is present at high levels in the membrane of nerve growth cones and proximal axon shafts. Membrane-associated forms of alpha- and beta-tubulin are the major phosphotyrosine-modified proteins in growth cone membranes in vivo. pp60c-src phosphorylates purified, unassembled tubulin subunits in vitro, inhibiting their ability to polymerize into microtubules. It is conceivable that tubulin phosphorylation by pp60c-src in the growth cone may regulate neurite extension by altering adhesion of cells to the substratum.