THE EXTRAORDINARY ACTIVE-SITE SUBSTRATE-SPECIFICITY OF PP60(C-SRC) - A MULTIPLE SPECIFICITY PROTEIN-KINASE
THE EXTRAORDINARY ACTIVE-SITE SUBSTRATE-SPECIFICITY OF PP60(C-SRC) - A MULTIPLE SPECIFICITY PROTEIN-KINASE
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DOI：
10.1074/jbc.270.10.5375
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发表时间：
1995-03-10
影响因子：
4.8
通讯作者：
LAWRENCE, DS
中科院分区：
文献类型：
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作者：
LEE, TR;NIU, JK;LAWRENCE, DS
我们报道了酪氨酸特异性蛋白激酶pp60（c-src）的第一个活性位点底物特异性分析。像camp依赖性蛋白激酶和蛋白激酶C一样，pp60（C -src）将磷酸化附着在活性位点导向肽上的各种非手性残基。此外，pp60（c-src）磷酸化芳香和脂肪醇。然而，pp60（c-src）的底物特异性比之前研究的两种丝氨酸/苏氨酸特异性蛋白激酶广泛得多。我们之前已经证明，camp依赖性蛋白激酶和蛋白激酶C都将利用广泛的非氨基酸残基作为底物，只要羟基部分和相邻肽主链之间的距离与丝氨酸和苏氨酸中的距离相当(Kwon, y - g。孟德洛，M.和劳伦斯，D. S.（1994）。相比之下，pp60（c-src）不会根据链长区分底物，它可以催化含有2-12个碳的残基的磷酸化，这些残基位于醇官能团和相邻肽键之间。此外，pp60（c-src）在活性位点导向肽中磷酸化l -丝氨酸，讨论了pp60（c-src）多重特异性的可能结构基础。最后，pp60（c-src）的活性位点特异性不仅限于l -氨基酸残基，而且还延伸到d -氨基酸领域。
We report the first active site substrate specificity analysis of a tyrosine-specific protein kinase, namely pp60(c-src). Like the cAMP-dependent protein kinase and protein kinase C, pp60(c-src) will phosphorylate an assortment of achiral residues attached to active site directed peptides. Furthermore, pp60(c-src) phosphorylates both aromatic and aliphatic alcohols. However, the substrate specificity of pp60(c-src) is much broader than that of the two previously examined serine/threonine-specific protein kinases. We have previously shown that both the cAMP-dependent protein kinase and protein kinase C will utilize a wide array of non-amino acid residues as substrates, as long as the distance between the hydroxyl moiety and the adjacent peptide backbone is comparable with that present in serine and threonine (Kwon, Y.-G., Mendelow, M., and Lawrence, D. S. (1994) J. Biol. Chem, 269, 4839-4844), In marked contrast, pp60(c-src) does not discriminate against substrates on the basis of chain length, catalyzing the phosphorylation of residues that contain anywhere from 2-12 carbons between the alcohol functional group and the adjacent peptide bond. In addition, pp60(c-src) phosphorylates L-serine in an active site-directed peptide, The possible structural basis for the multiple specificity of pp60(c-src) is discussed Finally, the active site specificity of pp60(c-src) is not just limited to L-amino acid residues, but also extends into the realm of D-amino acids as well.