The Galpha4 G protein subunit interacts with the MAP kinase ERK2 using a D-motif that regulates developmental morphogenesis in Dictyostelium.
The Galpha4 G protein subunit interacts with the MAP kinase ERK2 using a D-motif that regulates developmental morphogenesis in Dictyostelium.
复制标题
Galpha4 G 蛋白亚基使用 D 基序与 MAP 激酶 ERK2 相互作用，调节盘基网柄菌的发育形态发生。
DOI：
10.1016/j.ydbio.2009.09.011
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发表时间：
2009
影响因子：
2.7
通讯作者：
Hadwiger,JeffreyA
中科院分区：
文献类型：
--
作者：
Nguyen,Hoai-Nghia;Hadwiger,JeffreyA
G蛋白Gα亚基参与了盘基藻不同信号转导途径的特异性，但Gα亚基与效应子的相互作用尚未被证实。丝裂原活化蛋白激酶（MAP kinase，MAPK）对网骨藻Gα4亚基的激活有重要作用，并在该亚基上发现了一个MAPK对接位点（D-motif），提示Gα4亚基与MAPK之间可能存在相互作用。通过下拉和免疫共沉淀试验证明了Gα4亚基和ERK 2的体内结合。D基序的改变减少了Gα4亚基-ERK 2的相互作用，但对叶酸的反应仅轻微改变了MAPK的活化。在gα4−细胞中，具有改变的D基序的G α4亚基的表达允许蛞蝓形成，但不允许与顶点相关的形态发生。该突变体Gα4亚基的表达足以挽救对叶酸的趋化运动。D基序的改变也减少了与组成型活性Gα4亚基相关的聚集缺陷。这些结果表明，Gα4亚基-MAPK相互作用是必需的发育形态发生，但不是趋化叶酸。
G protein Gα subunits contribute to the specificity of different signal transduction pathways in Dictyostelium discoideum but Gα subunit-effector interactions have not been previously identified. The requirement of the Dictyostelium Gα4 subunit for MAP kinase (MAPK) activation and the identification of a putative MAPK docking site (D-motif) in this subunit suggested a possible interaction between the Gα4 subunit and MAPKs. In vivo association of the Gα4 subunit and ERK2 was demonstrated by pull-down and co-immunoprecipitation assays. Alteration of the D-motif reduced Gα4 subunit-ERK2 interactions but only slightly altered MAPK activation in response to folate. Expression of the Gα4 subunit with the altered D-motif in gα4−cells allowed for slug formation but not the morphogenesis associated with culmination. Expression of this mutant Gα4 subunit was sufficient to rescue chemotactic movement to folate. Alteration of the D-motif also reduced the aggregation defect associated with constitutively active Gα4 subunits. These results suggest Gα4 subunit-MAPK interactions are necessary for developmental morphogenesis but not for chemotaxis to folate.