DISTINCT REGIONS OF THE GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR ARE REQUIRED FOR TYROSINE PHOSPHORYLATION OF THE SIGNALING MOLECULES JAK2, STAT3, AND P42, P44(MAPK)
DISTINCT REGIONS OF THE GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR ARE REQUIRED FOR TYROSINE PHOSPHORYLATION OF THE SIGNALING MOLECULES JAK2, STAT3, AND P42, P44(MAPK)
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DOI：
10.1182/blood.v86.10.3698.bloodjournal86103698
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发表时间：
1995-11-15
期刊：
影响因子：
20.3
通讯作者：
LAYTON, LE
中科院分区：
文献类型：
--
作者：
NICHOLSON, SE;NOVAK, U;LAYTON, LE
粒细胞集落刺激因子 (G-CSF) 与其跨膜受体相互作用后，蛋白酪氨酸激酶 JAK1 和 JAK2 在酪氨酸上被磷酸化。Stat3 也是如此，转录激活剂 STAT 家族的成员被认为是由 JAK 激酶激活的。截短的 G-CSF 受体 (G-CSF-R) 突变体用于确定信号分子 JAK2、Stat3 和 p42、p44(MAPK) 的酪氨酸磷酸化，我们已经证明，G-CSF 诱导的 JAK2 酪氨酸磷酸化和激酶激活需要细胞质结构域的膜近端 57 个氨基酸，相反，最大 Stat3 酪氨酸磷酸化需要 G-CSF-R 细胞质结构域的氨基酸 96 至 183，Stat3 DNA 结合跨膜结构域截短 96 个氨基酸并含有单个酪氨酸残基的受体可能会发生这种情况，但与全长受体相比有所减少。与 Stat3 的酪氨酸磷酸化一起，这一发现表明全长受体中存在额外的 Stat3 结合位点。由于 G-CSF-R 在受体的羧基 126 氨基酸不存在的情况下可以发出促有丝分裂反应信号，因此 Stat3 似乎不是增殖所必需的，MAP 激酶酪氨酸磷酸化与增殖反应和 JAK2 激活相关。 (C) 1995 年，美国血液学会。
The protein tyrosine kinases JAK1 and JAK2 are phosphorylated on tyrosine after the interaction of granulocyte colony-stimulating factor (G-CSF) with its transmembrane receptor, So too is Stat3, a member of the STAT family of transcriptional activators thought to be activated by the JAK kinases, Truncated G-CSF receptor (G-CSF-R) mutants were used to determine the different regions of the cytoplasmic domain necessary for tyrosine phosphorylation of the signaling molecules JAK2, Stat3, and p42, p44(MAPK), We have shown that G-CSF-induced tyrosine phosphorylation and kinase activation of JAK2 requires the membrane proximal 57 amino acids of the cytoplasmic domain, In contrast, maximal Stat3 tyrosine phosphorylation required amino acids 96 to 183 of the G-CSF-R cytoplasmic domain, Stat3 DNA binding could occur with a receptor truncated 96 amino acids from the transmembrane domain and containing a single tyrosine residue, but was reduced in comparison with the full-length receptor. Together with the tyrosine phosphorylation of Stat3, this finding suggests that additional Stat3 binding sites are present in the full-length receptor, Because the G-CSF-R can signal a mitogenic response in the absence of the carboxyl-126 amino acids of the receptor, Stat3 does not appear to be required for proliferation, MAP kinase tyrosine phosphorylation correlated with both the proliferative response and JAK2 activation. (C) 1995 by The American Society of Hematology.