Nicholson S E, Novak U, Ziegler S F, Layton J E
Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Victoria Australia.
Blood. 1995 Nov 15;86(10):3698-704.
The protein tyrosine kinases JAK1 and JAK2 are phosphorylated 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, p44MAPK. 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 does not appear to be required for proliferation. MAP kinase tyrosine phosphorylation correlated with both the proliferative response and JAK2 activation.
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会发生酪氨酸磷酸化。转录激活因子STAT家族成员Stat3也是如此，它被认为是由JAK激酶激活的。截短的G-CSF受体（G-CSF-R）突变体被用于确定信号分子JAK2、Stat3以及p42、p44MAPK的酪氨酸磷酸化所必需的胞质结构域的不同区域。我们已经表明，G-CSF诱导的JAK2酪氨酸磷酸化和激酶激活需要胞质结构域的膜近端57个氨基酸。相比之下，Stat3酪氨酸的最大磷酸化需要G-CSF-R胞质结构域的96至183位氨基酸，Stat3的DNA结合可以发生在一个从跨膜结构域截短96个氨基酸且含有单个酪氨酸残基的受体上，但与全长受体相比有所减少。连同Stat3的酪氨酸磷酸化，这一发现表明增殖似乎并不需要额外的Stat3。丝裂原活化蛋白激酶（MAP激酶）的酪氨酸磷酸化与增殖反应和JAK2激活均相关。
