Biochemical characterization of a family of serine/threonine protein kinases regulated by tyrosine and serine/threonine phosphorylations.
Biochemical characterization of a family of serine/threonine protein kinases regulated by tyrosine and serine/threonine phosphorylations.
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DOI：
10.1016/s0021-9258(18)54918-8
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发表时间：
1991-10
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影响因子：
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通讯作者：
A. Rossomando;J. Sanghera;L. Marsden;Michael J. Weber;S. Pelech;T. Sturgill
中科院分区：
文献类型：
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作者：
A. Rossomando;J. Sanghera;L. Marsden;Michael J. Weber;S. Pelech;T. Sturgill
有丝分裂原激活的蛋白激酶(P42mapk)在血清饥饿的小鼠瑞士3T3细胞或EL4胸腺细胞与多种有丝分裂原一起处理后被瞬时激活。类似地，在1-甲基腺嘌呤诱导的海星卵母细胞成熟过程中，一个减数分裂激活的蛋白激酶(P44mpk)被激活。P42mapk和p44mpk都被鉴定为蛋白-丝氨酸/苏氨酸激酶，它们被磷酸化激活。由于同源蛋白激酶可能在有丝分裂和卵子发生中发挥重要作用，我们详细比较了这两种蛋白激酶的生化特性。我们发现，基于它们的体外底物特异性、对抑制剂的敏感性和免疫交叉反应，这些激酶是高度相关的。然而，它们的表观分子量不同，可以用色谱进行分离，这表明这两种酶是不同的。此外，在本研究过程中，我们在有丝分裂原刺激的瑞士小鼠3T3细胞和EL4胸腺细胞中鉴定出一种44 kDa的蛋白激酶，它与p44mpk共同纯化，因此似乎是海星酶的更近的同源物。对这些蛋白激酶的分析阐明了存在于有丝分裂原刺激细胞中的一组酪氨酸磷酸化的41-45 kDa蛋白质之间的关系(Martinez，R.，Nakamura.，K.D.和Weber，M.J.(1982)Mol.牢房。比奥尔。2,653-655；库珀，J.A.和亨特，T.(1984)Mol.牢房。比奥尔。4，30-37)，在表皮生长因子处理的瑞士小鼠3T3细胞中发现的两种髓鞘碱性蛋白激酶(Ahn，N.G.，Weel，J.E.，Chan，C.P.，和Krebs，E.G.(1990)J.Biol。化学。265、11487-11494)和p42mapk。我们的工作指出，存在一组相关的丝氨酸/苏氨酸蛋白激酶，受酪氨酸磷酸化调节，并在细胞周期的不同阶段发挥作用。
Mitogen-activated protein kinase (p42mapk) becomes transiently activated after treatment of serum-starved murine Swiss 3T3 cells or EL4 thymocytes with a diversity of mitogens. Similarly, a meiosis-activated protein kinase (p44mpk) becomes stimulated during maturation of sea star oocytes induced by 1-methyladenine. Both p42mapk and p44mpk have been identified as protein-serine/threonine kinases that are activated as a consequence of their phosphorylation. Because homologous protein kinases may play essential roles in both mitogenesis and oogenesis, we have compared in detail the biochemical properties of these two kinases. We find that these kinases are highly related based on their in vitro substrate specificities, sensitivity to inhibitors, and immunological cross-reactivity. However, they differ in apparent molecular weight and can be separated chromatographically, indicating that the two enzymes are distinct. Furthermore, in the course of this investigation, we have identified a 44-kDa protein kinase in mitogen-stimulated Swiss mouse 3T3 cells and EL4 thymocytes that co-purifies with p44mpk and thus appears to be a closer homolog of the sea star enzyme. Analysis of these protein kinases clarifies the relationships between a set of tyrosine-phosphorylated 41-45-kDa proteins present in mitogen-stimulated cells (Martinez, R., Nakamura., K. D., and Weber, M. J. (1982) Mol. Cell. Biol. 2, 653-655; Cooper, J. A., and Hunter, T. (1984) Mol. Cell. Biol. 4, 30-37), two myelin basic protein kinases identified in epidermal growth factor-treated Swiss mouse 3T3 cells (Ahn, N. G., Weiel, J. E., Chan, C. P., and Krebs, E. G. (1990) J. Biol. Chem. 265, 11487-11494), and p42mapk. Our work points to the existence of a group of related serine/threonine protein kinases, regulated by tyrosine phosphorylation and functioning at different stages of the cell cycle.