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首页> 外文期刊>Molecular and Cellular Biology >JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region.
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JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region.

机译：JAK2与粒细胞-巨噬细胞集落刺激因子受体的βc链相关，其激活需要膜近端区域。

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The high-affinity receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a unique alpha chain and a beta c subunit that is shared with the receptors for interleukin-3 (IL-3) and IL-5. Two regions of the beta c chain have been defined; these include a membrane-proximal region of the cytoplasmic domain that is required for mitogenesis and a membrane-distal region that is required for activation of Ras, Raf-1, mitogen-activated protein kinase, and S6 kinase. Recent studies have implicated the cytoplasmic protein tyrosine kinase JAK2 in signalling through a number of the cytokine receptors, including the IL-3 and erythropoietin receptors. In the studies described here, we demonstrate that GM-CSF stimulation of cells induces the tyrosine phosphorylation of JAK2 and activates its in vitro kinase activity. Mutational analysis of the beta c chain demonstrates that only the membrane-proximal 62 amino acids of the cytosolic domain are required for JAK2 activation. Thus, JAK2 activation is correlated with induction of mitogenesis but does not, alone, activate the Ras pathway. Carboxyl truncations of the alpha chain, which inactivate the receptor for mitogenesis, are unable to mediate GM-CSF-induced JAK2 activation. Using baculovirus-expressed proteins, we further demonstrate that JAK2 physically associates with the beta c chain but not with the alpha chain. Together, the results further support the hypothesis that the JAK family of kinase are critical to coupling cytokine binding to tyrosine phosphorylation and ultimately mitogenesis.
机译：粒细胞巨噬细胞集落刺激因子（GM-CSF）的高亲和力受体由独特的α链和与白介素3（IL-3）和IL-5受体共享的βc亚基组成。已经定义了βc链的两个区域。这些包括有丝分裂发生所需的胞质结构域的膜近端区域和激活Ras，Raf-1，有丝分裂原活化的蛋白激酶和S6激酶所需的膜远端区域。最近的研究已经暗示细胞质蛋白酪氨酸激酶JAK2通过许多细胞因子受体，包括IL-3和促红细胞生成素受体进行信号传导。在此处描述的研究中，我们证明了细胞的GM-CSF刺激诱导JAK2的酪氨酸磷酸化并激活其体外激酶活性。 βc链的突变分析表明，JAK2激活仅需要胞质域的膜近62个氨基酸。因此，JAK2激活与有丝分裂的诱导相关，但并不单独激活Ras途径。灭活有丝分裂受体的α链的羧基截短不能介导GM-CSF诱导的JAK2激活。使用杆状病毒表达的蛋白质，我们进一步证明JAK2在物理上与βc链相关，但与α链无关。总之，这些结果进一步支持了以下假设：激酶的JAK家族对于将细胞因子结合至酪氨酸磷酸化以及最终促有丝分裂至关重要。

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