Calcium- and lipid-independent protein kinase C autophosphorylation. Activation by low pH.
The activity of protein kinase C is dependent on communication between a catalytic domain and a Ca2+- and lipid-binding regulatory domain in the kinase molecule. It is shown here that acidic reaction conditions can bypass the calcium and lipid requirement in the autophosphorylation of protein kinase C. Acidic pH does not entirely deregulate the kinase, though, since only autophosphorylation is favored between pH 4 and 6 and not the phosphorylation of alternative substrate proteins. Interestingly, low pH stably activated protein kinase C: when restored to neutral pH, the autophosphorylation reaction remained independent of Ca2+ and lipid. These observations suggest that protonation of functional groups in the protein kinase C molecule, with their pKa suggestive of histidine imidazole, can produce a stable conformation where regulatory constraints on enzyme activity have been removed.
McFadden
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PN
Department of Biochemistry, University of California, Berkeley 94720.
Mandpe
A
A
Koshland
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DE
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002417:Cattle; D004789:Enzyme Activation; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008055:Lipids / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D008055:Lipids; D011493:Protein Kinase C; D002118:Calcium