Protein kinase C phosphorylated at a conserved threonine is retained in the cytoplasm.
Phosphorylation of calcium-activated protein kinase Cs (PKCs) at threonine 634 and/or threonine 641 increases during long term potentiation or associative learning in rodents. In the marine mollusk Aplysia, persistent activation of the calcium-activated PKC Apl I occurs during long term facilitation. We have raised an antibody to a peptide from PKC Apl I phosphorylated at threonines 613 and 620 (sites homologous to threonines 634 and 641). This antibody recognizes PKC Apl I only when it is phosphorylated at threonine 613. Both phorbol esters and serotonin increase the percentage of kinase phosphorylated at threonine 613 in Aplysia neurons. Furthermore, the pool of PKC that is phosphorylated at threonine 613 in neurons is resistant to both membrane translocation and down-regulation. Replacement of threonine 613 with alanine increased the affinity of PKC Apl I for calcium, suggesting that phosphorylation of this site may reduce the ability of PKC Apl I to translocate to membranes in the presence of calcium. We propose that phosphorylation of this site is important for removal of PKC from the membrane and may be a mechanism for negative feedback of PKC activation.
Nakhost
A
A
Department of Neurology, McGill University, Montreal Neurological Institute, Montreal, Quebec H3A 2B4, Canada.
Dyer
J R
JR
Pepio
A M
AM
Fan
X
X
Sossin
W S
WS
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001048:Aplysia; D002118:Calcium / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010748:Phosphopeptides / Q000276:immunology; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism*; D011493:Protein Kinase C / Q000737:chemistry* / Q000276:immunology; D012701:Serotonin / Q000494:pharmacology; D013912:Threonine / Q000737:chemistry*
D000906:Antibodies; D010748:Phosphopeptides; D010769:Phosphothreonine; D013912:Threonine; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D002118:Calcium