ATYPICAL XI-PROTEIN KINASE-C DISPLAYS A UNIQUE DEVELOPMENTAL EXPRESSION PATTERN IN RAT-BRAIN

The expression of atypical zeta-protein kinase C (PKC) was examined du ring prenatal and postnatal rat brain development. Immunoblot as well as transcript analysis revealed a dramatic increase in expression at 2 -3 days post-birth, which declined thereafter and remained at levels o bserved in the adult brain. The expression of zeta-PKC precedes that o f the other PKC isoforms in developing rat brain. Subcellular fraction ation of pup and adult brain documented distribution between all three distinct fractions (A,B,C), including the low speed pellet composed o f nuclei. In adult brain, the kinase was enriched in the A fraction of the sucrose gradient. Specific substrate proteins of zeta-PKC were ch aracterized in each of the subcellular fractions from both pup and adu lt brain. Four predominant proteins pp76, pp60-doublet, pp54 and pp45 were identified as zeta-PKC endogenous substrates. All four proteins w ere phosphorylated on serine residues, while the pp60-doublet was also phosphorylated on tyrosine. The pp60-doublet was the most predominant substrate, specifically enriched in the A fraction of a sucrose gradi ent of adult brain and immunoprecipitated by monoclonal antibody to pp 60(c-src).