S-100 and other acidic proteins promote Ca2+-independent phosphorylation of protamine catalyzed by a new protein kinase from brain.
A new protein kinase modulated by S-100 (tentatively referred to as protein kinase X) was partially purified from pig brain extracts. The activity of protein kinase X, which was independent of Ca2+, was demonstrated when protamine (free base), but not protamine sulfate and other proteins (including histone), was used as substrate. The enzyme activity, found to distribute in both soluble and particulate fractions and to occur at the highest level in brain compared with other tissues (heart, kidney, liver, skeletal muscle, spleen, and testis) of rats, was also modulated by other acidic proteins (calmodulin, troponin C, and stimulatory modulator) in a Ca2+ -independent manner. S-100 and other acidic proteins appeared to function as "substrate modifiers" by interacting with protamine (a highly basic protein), but not with the enzyme, thus rendering protamine in the complex a superior phosphate acceptor. The two isoforms of S-100 (i.e., a and b) were equally effective. Although the enzyme was not inhibited by many agents (trifluoperazine, melittin, cytotoxin I, polymyxin B, and spermine) shown to inhibit markedly phospholipid/Ca2+- or calmodulin/Ca2+ -stimulated protein kinase, gossypol was found to inhibit specifically protein kinase X. The present findings suggest that S-100, a major acidic protein specific to nervous system, may promote phosphorylation by protein kinase X of certain neural proteins resembling protamine or containing protamine-like domains, in addition to its presumed role of a low-affinity Ca2+ -binding protein.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011479:Protamines / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity; D013552:Swine; D014018:Tissue Distribution
D006657:Histones; D009419:Nerve Tissue Proteins; D011479:Protamines; D009418:S100 Proteins; D011494:Protein Kinases; D002118:Calcium