Developmental regulation of protein tyrosine phosphorylation in rat brain.

Proteins phosphorylated at tyrosine residues in the developing rat brain have been identified with a focus on the nerve growth cone and synaptic terminal. Endogenous protein phosphorylation in membranes from a subcellular growth cone fraction of fetal rat brain revealed prominent 55-60 kD phosphotyrosine-containing proteins. Proteins of similar size were recognized by phosphotyrosine antibodies in isolated growth cone membranes, indicating that they contained phosphotyrosine in vivo. Proteins of 55-60 kD were not highly phosphorylated in synaptosomes from adult brain, suggesting a growth cone-specific function. Generally, tyrosine phosphorylation was much lower in adult brain than in fetal brain fractions. Although some synaptosomal membrane proteins that contained phosphotyrosine corresponded in size with those in growth cone membranes (92 kD, 41 kD), others were unique to synaptosomal membranes (38 kD and 30 kD). Immunoperoxidase staining of fetal rat neocortex with phosphotyrosine antibodies at embryonic day 19 revealed immunoreactivity in presumptive migratory neuroblasts in the intermediate zone and in processes of the molecular layer. Proliferating neuroepithelial cells of the ventricular zone showed little immunoreactivity. Lower levels of phosphotyrosine immunoreactivity were seen until postnatal day 10, correlating with the period of maximal process outgrowth. These results indicate that protein tyrosine phosphorylation in the developing nervous system may be functionally significant in an aspect of neuronal differentiation such as growth cone-mediated process extension and cell migration. An analogous role in the mature brain may be related to synaptic plasticity or function.