MAPK signaling to the early secretory pathway revealed by kinase/phosphatase functional screening

被引：146

作者：

Farhan, Hesso ^{[1
]}

Wendeler, Markus W. ^{[1
]}

Mitrovic, Sandra ^{[1
]}

Fava, Eugenio ^{[2
]}

Silberberg, Yael ^{[4
]}

Sharan, Roded ^{[4
]}

Zerial, Marino ^{[3
]}

Hauri, Hans-Peter ^{[1
]}

机构：

[1] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland

[2] High Throughput Technol Dev Studio, D-01307 Dresden, Germany

[3] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany

[4] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel

来源：

JOURNAL OF CELL BIOLOGY | 2010年 / 189卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

RETICULUM EXIT SITES; GOLGI FRAGMENTATION; CELL-MIGRATION; HUMAN KINASES; CIS-SIDE; PROTEIN; ER; TRANSPORT; COMPLEX; EXPORT;

D O I：

10.1083/jcb.200912082

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

To what extent the secretory pathway is regulated by cellular signaling is unknown. In this study, we used RNA interference to explore the function of human kinases and phosphatases in controlling the organization of and trafficking within the secretory pathway. We identified 122 kinases/phosphatases that affect endoplasmic reticulum (ER) export, ER exit sites (ERESs), and/or the Golgi apparatus. Numerous kinases/phosphatases regulate the number of ERESs and ER to Golgi protein trafficking. Among the pathways identified, the Raf-MEK (MAPK/ERK [extracellular signal-regulated kinase] kinase)-ERK cascade, including its regulatory proteins CNK1 (connector enhancer of the kinase suppressor of Ras-1) and neurofibromin, controls the number of ERESs via ERK2, which targets Sec16, a key regulator of ERESs and COPII (coat protein II) vesicle biogenesis. Our analysis reveals an unanticipated complexity of kinase/phosphatase-mediated regulation of the secretory pathway, uncovering a link between growth factor signaling and ER export.

引用

页码：997 / 1011

页数：15

共 51 条

[1] ERK1-/- mice exhibit Th1 cell polarization and increased susceptibility to experimental autoimmune encephalomyelitis [J].