JUN IS PHOSPHORYLATED BY SEVERAL PROTEIN-KINASES AT THE SAME SITES THAT ARE MODIFIED IN SERUM-STIMULATED FIBROBLASTS
JUN IS PHOSPHORYLATED BY SEVERAL PROTEIN-KINASES AT THE SAME SITES THAT ARE MODIFIED IN SERUM-STIMULATED FIBROBLASTS
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DOI：
10.1128/mcb.12.10.4694
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发表时间：
1992-10-01
影响因子：
5.3
通讯作者：
ABATE, C
中科院分区：
文献类型：
--
作者：
BAKER, SJ;KERPPOLA, TK;ABATE, C
c-jun是立即早期基因家族的成员，其表达由诸如血清刺激、佛波酯和分化信号的因素诱导。在这里，我们表明，增加Jun合成血清刺激后，伴随着磷酸化的增加。评价了几种丝氨酸-苏氨酸激酶在体外磷酸化Jun的能力。p34 cdc 2、蛋白激酶C、酪蛋白激酶II和pp 44 mapk有效地磷酸化Jun，而环AMP依赖性蛋白激酶和糖原合成酶激酶III则不能。p34 cdc 2磷酸化位点与体内血清诱导后的磷酸化位点相似。磷酸化的主要位点定位于丝氨酸63、73和246。用几种激酶磷酸化全长Jun不影响Jun同源二聚体或Fos-Jun异源二聚体的DNA结合活性。比较野生型和突变型蛋白质的DNA结合和体外转录特性，这些蛋白质含有丙氨酸或天冬氨酸残基代替Ser-63，-73和-246，发现同源二聚体复合物之间只有微小的差异，而Fos-Jun异源二聚体之间没有差异。因此，磷酸化的Jun没有产生显着的变化，在二聚化，DNA结合，或在体外转录活性。磷酸化在调节Jun功能中的调节作用可能比以前提出的要复杂得多。
c-jun is a member of the family of immediate-early genes whose expression is induced by factors such as serum stimulation, phorbol ester, and differentiation signals. Here we show that increased Jun synthesis after serum stimulation is accompanied by a concomitant increase in phosphorylation. Several serine-threonine kinases were evaluated for their ability to phosphorylate Jun in vitro. p34cdc2, protein kinase C, casein kinase II, and pp44mapk phosphorylated Jun efficiently, whereas cyclic AMP-dependent protein kinase and glycogen synthase kinase III did not. The sites phosphorylated by p34cdc2 were similar to those phosphorylated in vivo after serum induction. The major sites of phosphorylation were mapped to serines 63, 73, and 246. Phosphorylation of full-length Jun with several kinases did not affect the DNA-binding activity of Jun homodimers or Fos-Jun heterodimers. Comparison of the DNA binding and in vitro transcription properties of wild-type and mutated proteins containing either alanine or aspartic acid residues in place of Ser-63, -73, and -246 revealed only minor differences among homodimeric complexes and no differences among Fos-Jun heterodimers. Thus, phosphorylation of Jun did not produce a significant change in dimerization, DNA-binding, or in vitro transcription activity. The regulatory role of phosphorylation in the modulation of Jun function is likely to be considerably more complex than previously suggested.