Phosphorylation of RGS regulates MAP kinase localization and promotes completion of cytokinesis.
Phosphorylation of RGS regulates MAP kinase localization and promotes completion of cytokinesis.
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DOI：
10.26508/lsa.202101245
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发表时间：
2022-10
影响因子：
4.4
通讯作者：
Kelley, Joshua B.
中科院分区：
文献类型：
--
作者：
Simke, William C.;Johnson, Cory P.;Hart, Andrew J.;Mayhue, Sari;Craig, P. Lucas;Sojka, Savannah;Kelley, Joshua B.
RGS Sst2的磷酸化改变了它的亚细胞分布、MAPK定位以及与Kel1的相互作用，从而促进了极化生长与细胞质分裂的完成。酵母利用G蛋白偶联受体信号通路来检测和跟踪交配信息素。G蛋白偶联受体途径受到G蛋白信号转导调节因子Sst2的抑制，Sst2诱导GαGTP酶活性和下游信号失活。G蛋白信号激活MAPK Fus3，使RGS磷酸化；然而，这种修饰的作用尚不清楚。我们发现信息素诱导的RGS磷酸化高峰提前，RGS的磷酸化状态控制其定位并影响MAPK的空间分布。令人惊讶的是，RGS的磷酸化在信息素诱导生长之前促进了细胞质分裂的完成。在信息素存在的情况下，胞质分裂的完成由kelch重复蛋白Kel1促进，并被Forin Bni1拮抗。我们发现RGS与Kel1形成络合物，并且更喜欢不可磷酸化的RGS突变体。我们还发现，不可磷酸化的RGS的过度表达会加剧细胞动力学缺陷，而Kel1的过度表达可以挽救它们。这些数据将我们引导到一个模型，在这个模型中，Kel1在信息素诱导的极性之前促进细胞质分裂的完成，但被非磷酸化的RGS结合抑制。
Phosphorylation of the RGS Sst2 alters its subcellular distribution, MAPK localization, and interaction with Kel1, which promotes coordination of polarized growth with completion of cytokinesis. Yeast use the G-protein–coupled receptor signaling pathway to detect and track the mating pheromone. The G-protein–coupled receptor pathway is inhibited by the regulator of G-protein signaling (RGS) Sst2 which induces Gα GTPase activity and inactivation of downstream signaling. G-protein signaling activates the MAPK Fus3, which phosphorylates the RGS; however, the role of this modification is unknown. We found that pheromone-induced RGS phosphorylation peaks early; the phospho-state of RGS controls its localization and influences MAPK spatial distribution. Surprisingly, phosphorylation of the RGS promotes completion of cytokinesis before pheromone-induced growth. Completion of cytokinesis in the presence of pheromone is promoted by the kelch-repeat protein, Kel1 and antagonized by the formin Bni1. We found that RGS complexes with Kel1 and prefers the unphosphorylatable RGS mutant. We also found overexpression of unphosphorylatable RGS exacerbates cytokinetic defects, whereas they are rescued by overexpression of Kel1. These data lead us to a model where Kel1 promotes completion of cytokinesis before pheromone-induced polarity but is inhibited by unphosphorylated RGS binding.
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影响因子：
21.3
作者：
Amaral, Nuno;Vendrell, Alexandre;Mendoza, Manuel
通讯作者：
Mendoza, Manuel
DOI：
10.1074/jbc.r116.714980
发表时间：
2016-04-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Alvaro CG;Thorner J
通讯作者：
Thorner J
影响因子：
3.3
作者：
Errede B;Vered L;Ford E;Pena MI;Elston TC
通讯作者：
Elston TC
影响因子：
9.2
作者：
Dyer, Jayme M.;Savage, Natasha S.;Jin, Meng;Zyla, Trevin R.;Elston, Timothy C.;Lew, Daniel J.
通讯作者：
Lew, Daniel J.
影响因子：
5.3
作者：
CHAN, RK;OTTE, CA
通讯作者：
OTTE, CA