Phosphorylation of proteins of the postsynaptic density: effect of development on protein tyrosine kinase and phosphorylation of the postsynaptic density glycoprotein, PSD-GP180.

The effect of development on the tyrosine kinase activity of postsynaptic densities (PSDs) has been determined. PSDs were prepared from the forebrains of rats ranging in postnatal age from 13 to 90 days and the phosphorylation of both exogenous and endogenous substrates by tyrosine kinase measured. PSDs exhibited tyrosine kinase activity at all ages examined. Phosphorylation of the exogenous substrates polyglutamyltyrosine (4:1) and [val5] angiotensin II increased twofold between days 17 and 22 and then decreased between days 30 and 90 to levels slightly lower than those present at 13 days. The phosphorylation of endogenous PSD proteins on tyrosine residues, assessed by alkali digestion of polyacrylamide gels of 32P-labelled PSD proteins and by measuring the formation of [32P] phosphotyrosine by PSDs incubated in the presence of [gamma-32P] ATP, closely paralleled the changes in total tyrosine kinase activity. Tyrosine phosphorylation of the PSD-specific glycoprotein, PSD-GP180, also showed a transient increase between days 22 and 30, although its concentration within the PSD continued to increase slowly up to 90 days. The results indicate that the tyrosine kinase activity of PSDs is developmentally regulated and that tyrosine phosphorylation of PSD proteins is limited by enzyme rather than substrate availability.