The two major phosphoproteins in growth cones are probably identical to two protein kinase C substrates correlated with persistence of long-term potentiation.
Regulation of neural protein kinase C (PKC) activity appears to directly affect the persistence of long-term potentiation (LTP; Akers and Routtenberg, 1985; Lovinger et al., 1985, 1986, 1987; Routtenberg et al., 1985, 1986; Akers et al., 1986; Linden et al., 1987), a model of neural plasticity (Bliss and Lomo, 1973). In addition, the in vitro phosphorylation of a brain-specific PKC substrate, protein F1 (Mr 47 kDa, pl 4.5), has been directly correlated with persistence of LTP (Lovinger et al., 1986). Because PKC has been implicated in neurite outgrowth and is present at high levels in growth cone-rich areas of fetal brain, we investigated and characterized PKC substrates in a preparation of isolated nerve growth cone fragments from fetal rat brain and compared them with PKC substrates found in adult rat hippocampus. Four major proteins in the growth cone preparation showed endogenous phosphorylation levels at least 10-fold greater than any other phosphoproteins. Three of these 4 phosphoproteins, termed pp40, pp46, and pp80 (Katz et al., 1985), were phosphorylated by exogenous PKC in a dose-dependent manner, indicating that PKC activity might be of particular importance relative to other kinases in growth cone function. The 2 most highly labeled PKC substrates, pp46 and pp80, comigrated on 2-dimensional gels with the adult hippocampal proteins F1 and "80k" (Mr 78-80 kDa, pl 4.0), respectively. In addition, similarities in charge heterogeneity, 2-dimensional phosphopeptide maps, and increased phosphorylation in the presence of exogenous PKC or PKC stimulators suggest that protein F1 and 80k are highly homologous to, if not identical to, pp46 and pp80, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Nelson
R B
RB
Cresap Neuroscience Laboratory, Northwestern University, Evanston, Illinois 60201.
Linden
D J
DJ
Hyman
C
C
Pfenninger
K H
KH
Routtenberg
A
A
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D015180:Electrophoresis, Gel, Two-Dimensional; D004594:Electrophysiology; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010449:Peptide Mapping; D010718:Phosphatidylserines / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
D009419:Nerve Tissue Proteins; D010718:Phosphatidylserines; D010750:Phosphoproteins; D011493:Protein Kinase C