Seger R, Ahn N G, Boulton T G, Yancopoulos G D, Panayotatos N, Radziejewska E, Ericsson L, Bratlien R L, Cobb M H, Krebs E G
Department of Pharmacology, University of Washington, Seattle 98195.
Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6142-6. doi: 10.1073/pnas.88.14.6142.
Microtubule-associated protein 2 kinase (MAP kinase), which exists in several forms, is a protein serine/threonine kinase that participates in a growth factor-activated protein kinase cascade in which it activates a ribosomal protein S6 kinase (pp90rsk) while being regulated itself by a cytoplasmic factor (MAP kinase activator). Experiments with recombinant MAP kinase, ERK2, purified from Escherichia coli in a nonactivated form revealed a self-catalyzed phosphate incorporation into both tyrosine and threonine residues. Another MAP kinase, ERK1, purified from insulin-stimulated cells also autophosphorylated on tyrosine and threonine residues. Autophosphorylation of ERK2 correlated with its autoactivation, although both autophosphorylation and autoactivation were slow compared to that occurring in the presence of MAP kinase activator. Therefore, we propose that autophosphorylation is probably involved in the MAP kinase activation process in vitro, but it may not be sufficient for full activation. The specificity toward tyrosine and threonine residues indicates that the MAP kinases ERK1 and ERK2 are members of a group of kinases with specificity for tyrosine as well as serine and threonine residues.
微管相关蛋白2激酶（MAP激酶）有多种形式，是一种蛋白丝氨酸/苏氨酸激酶，参与生长因子激活的蛋白激酶级联反应，在该反应中它激活核糖体蛋白S6激酶（pp90rsk），同时自身受一种细胞质因子（MAP激酶激活剂）调控。用从大肠杆菌中以非激活形式纯化得到的重组MAP激酶ERK2进行的实验显示，它能自我催化将磷酸基团掺入酪氨酸和苏氨酸残基。从胰岛素刺激的细胞中纯化得到的另一种MAP激酶ERK1也能在酪氨酸和苏氨酸残基上进行自身磷酸化。ERK2的自身磷酸化与其自身激活相关，尽管与在MAP激酶激活剂存在时发生的情况相比，自身磷酸化和自身激活都很缓慢。因此，我们提出自身磷酸化可能在体外MAP激酶激活过程中起作用，但可能不足以实现完全激活。对酪氨酸和苏氨酸残基的特异性表明，MAP激酶ERK1和ERK2是一组对酪氨酸以及丝氨酸和苏氨酸残基具有特异性的激酶成员。
