A human MAP kinase interactome

被引：160

作者：

Bandyopadhyay, Sourav ^{[1
,2
,3
]}

Chiang, Chih-yuan ^{[4
]}

Srivastava, Jyoti ^{[5
]}

Gersten, Merril ^{[1
,2
,3
]}

White, Suhaila ^{[4
]}

Bell, Russell ^{[6
]}

Kurschner, Cornelia ^{[6
]}

Martin, Christopher H. ^{[6
]}

Smoot, Mike ^{[1
,2
]}

Sahasrabudhe, Sudhir ^{[6
]}

Barber, Diane L. ^{[5
]}

Chanda, Sumit K. ^{[4
]}

Ideker, Trey ^{[1
,2
,3
,7
]}

机构：

[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Program Bioinformat, La Jolla, CA 92093 USA

[4] Novartis Res Fdn, Genom Inst, San Diego, CA USA

[5] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA

[6] Prolexys Pharmaceut Inc, Salt Lake City, UT USA

[7] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

来源：

NATURE METHODS | 2010年 / 7卷 / 10期

基金：

美国国家卫生研究院;

关键词：

ACTIVATED PROTEIN-KINASE; H EXCHANGER NHE1; SACCHAROMYCES-CEREVISIAE; INTERACTION NETWORK; SYSTEMS BIOLOGY; GLOBAL ANALYSIS; YEAST; PATHWAYS; PHOSPHORYLATION; ORGANIZATION;

D O I：

10.1038/NMETH.1506

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps.

引用

页码：801 / U50

页数：7

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