Efficient termination of vacuolar Rab GTPase signaling requires coordinated action by a GAP and a protein kinase.
Efficient termination of vacuolar Rab GTPase signaling requires coordinated action by a GAP and a protein kinase.
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DOI：
10.1083/jcb.200801001
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发表时间：
2008-09-22
影响因子：
7.8
通讯作者：
Merz, Alexey J.
中科院分区：
文献类型：
--
作者：
Brett, Christopher L.;Plemel, Rachael L.;Lobinger, Braden T.;Vignali, Marissa;Fields, Stanley;Merz, Alexey J.
Rab鸟苷三磷酸酶（GTPases）是膜特性和动力学的关键调节剂，但控制Rab信号传导的体内途径定义不清。在这里，我们表明，GTP酶激活蛋白Gyp 7在体内灭活酵母液泡Rab Ypt 7。为了有效地终止Ypt 7信号传导，Gyp 7需要来自抑制性酪蛋白激酶I Yck 3的下游辅助。Yck 3介导至少两个Ypt 7信号传导靶点的磷酸化：系链，Vps-C/同型融合和液泡蛋白分选（HOPS）亚基Vps 41，以及SNARE，Vam 3。两种底物的磷酸化被Ypt 7-三磷酸鸟苷（GTP）所对抗。我们进一步证明，Ypt 7结合不是一个，而是两个Vps-C/HOPS亚基：Vps 39，一个假定的Ypt 7核苷酸交换因子，和Vps 41。因此，Gyp 7刺激的Ypt 7上的GTP水解似乎触发Ypt 7信号传导的被动终止和Ypt 7下游靶标的主动激酶介导的抑制。我们建议，通过Ypt 7通路的信号传播是由集成的反馈和前馈回路控制。在这个模型中，Yck 3在对接和融合中强制要求激活Rab。
Rab guanosine triphosphatases (GTPases) are pivotal regulators of membrane identity and dynamics, but the in vivo pathways that control Rab signaling are poorly defined. Here, we show that the GTPase-activating protein Gyp7 inactivates the yeast vacuole Rab Ypt7 in vivo. To efficiently terminate Ypt7 signaling, Gyp7 requires downstream assistance from an inhibitory casein kinase I, Yck3. Yck3 mediates phosphorylation of at least two Ypt7 signaling targets: a tether, the Vps-C/homotypic fusion and vacuole protein sorting (HOPS) subunit Vps41, and a SNARE, Vam3. Phosphorylation of both substrates is opposed by Ypt7-guanosine triphosphate (GTP). We further demonstrate that Ypt7 binds not one but two Vps-C/HOPS subunits: Vps39, a putative Ypt7 nucleotide exchange factor, and Vps41. Gyp7-stimulated GTP hydrolysis on Ypt7 therefore appears to trigger both passive termination of Ypt7 signaling and active kinase-mediated inhibition of Ypt7's downstream targets. We propose that signal propagation through the Ypt7 pathway is controlled by integrated feedback and feed-forward loops. In this model, Yck3 enforces a requirement for the activated Rab in docking and fusion.
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影响因子：
9.2
作者：
Bone, N;Millar, JBA;Armstrong, J
通讯作者：
Armstrong, J
跨节相互作用引起酵母液泡腔的Ca2+外排。
影响因子：
7.8
作者：
Merz, AJ;Wickner, WT
通讯作者：
Wickner, WT
影响因子：
11.4
作者：
Kleijnen, Maurits F.;Kirkpatrick, Donald S.;Gygi, Steven P.
通讯作者：
Gygi, Steven P.
影响因子：
11.8
作者：
Peplowska, Karolina;Markgraf, Daniel F.;Ungermann, Christian
通讯作者：
Ungermann, Christian
影响因子：
64.8
作者：
Nichols, BJ;Ungermann, C;Haas, A
通讯作者：
Haas, A