The atypical protein kinase C in Aplysia can form a protein kinase M by cleavage.
In vertebrates, a brain-specific transcript from the atypical protein kinase C (PKC) zeta gene encodes protein kinase M (PKM) zeta, a constitutively active kinase implicated in the maintenance of synaptic plasticity and memory. We have cloned the atypical PKC from Aplysia, PKC Apl III. We did not find a transcript in Aplysia encoding PKMzeta, and evolutionary analysis of atypical PKCs suggests formation of this transcript is restricted to vertebrates. Instead, over-expression of PKC Apl III in Aplysia sensory neurons leads to production of a PKM fragment of PKC Apl III. This cleavage was induced by calcium and blocked by calpain inhibitors. Moreover, nervous system enriched spliced forms of PKC Apl III show enhanced cleavage. PKC Apl III could also be activated through phosphorylation downstream of phosphoinositide 3-kinase. We suggest that PKM forms of atypical PKCs play a conserved role in memory formation, but the mechanism of formation of these kinases has changed over evolution.
Bougie
Joanna K
JK
Department of Psychology, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Lim
Travis
T
Farah
Carole Abi
CA
Manjunath
Varsha
V
Nagakura
Ikue
I
Ferraro
Gino B
GB
Sossin
Wayne S
WS
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008845:Microinjections; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity / Q000187:drug effects; D010766:Phosphorylation; D011493:Protein Kinase C / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology
D012701:Serotonin; D004247:DNA; D011493:Protein Kinase C; D002154:Calpain