Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Cζ (PKCζ) and regulates PKCξ activity

被引:68
作者
Liu, XF [1 ]
Ishida, H [1 ]
Raziuddin, R [1 ]
Miki, T [1 ]
机构
[1] NCI, Basic Res Lab, Mol Tumor Biol Sect, Bethesda, MD 20892 USA
关键词
D O I
10.1128/mcb.24.15.6665-6675.2004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regulation of cell polarity is an important biological event that governs diverse cell functions such as localization of embryonic determinants and establishment of tissue and organ architecture. The Rho family GTPases and the polarity complex Par6/Par3/atypical protein kinase C (PKC) play a key role in the signaling pathway, but the molecules that regulate upstream signaling are still not known. Here we identified the guanine nucleotide exchange factor ECT2 as an activator of the polarity complex. ECT2 interacted with Par6 as well as Par3 and PKCzeta. Coexpression of Par6 and ECT2 efficiently activated Cdc42 in vivo. Overexpression of ECT2 also stimulated the PKC activity, whereas dominant-negative ECT2 inhibited the increase in PKCzeta activity stimulated by Par6. ECT2 localization was detected at sites of cell-cell contact as well as in the nucleus of MDCK cells. The expression and localization of ECT2 were regulated by calcium, which is a critical regulator of cell-cell adhesion. Together, these results suggest that ECT2 regulates the polarity complex Par6/Par3/PKCzeta and possibly plays a role in epithelial cell polarity.
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收藏
页码:6665 / 6675
页数:11
相关论文
共 43 条
[11]  
Johansson AS, 2000, J CELL SCI, V113, P3267
[12]   E-cadherin-mediated cell-cell attachment activates Cdc42 [J].
Kim, SH ;
Li, ZG ;
Sacks, DB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (47) :36999-37005
[13]   Accumulation of GTP-bound RhoA during cytokinesis and a critical role of ECT2 in this accumulation [J].
Kimura, K ;
Tsuji, T ;
Takada, Y ;
Miki, T ;
Narumiya, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (23) :17233-17236
[14]   Composition and formation of intercellular junctions in epithelial cells [J].
Knust, E ;
Bossinger, O .
SCIENCE, 2002, 298 (5600) :1955-1959
[15]   A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity [J].
Lin, D ;
Edwards, AS ;
Fawcett, JP ;
Mbamalu, G ;
Scott, JD ;
Pawson, T .
NATURE CELL BIOLOGY, 2000, 2 (08) :540-547
[16]   Modes of protein movement that lead to the asymmetric localization of partner of numb during Drosophila neuroblast division [J].
Lu, BW ;
Ackerman, L ;
Jan, LY ;
Jan, YN .
MOLECULAR CELL, 1999, 4 (06) :883-891
[17]   Regulation of the movement of solutes across tight junctions [J].
Madara, JL .
ANNUAL REVIEW OF PHYSIOLOGY, 1998, 60 :143-159
[18]   Small GTPases take the stage [J].
Manser, E .
DEVELOPMENTAL CELL, 2002, 3 (03) :323-328
[19]   ONCOGENE ECT2 IS RELATED TO REGULATORS OF SMALL GTP-BINDING PROTEINS [J].
MIKI, T ;
SMITH, CL ;
LONG, JE ;
EVA, A ;
FLEMING, TP .
NATURE, 1993, 362 (6419) :462-465
[20]   EXPRESSION CDNA CLONING OF THE KGF RECEPTOR BY CREATION OF A TRANSFORMING AUTOCRINE LOOP [J].
MIKI, T ;
FLEMING, TP ;
BOTTARO, DP ;
RUBIN, JS ;
RON, D ;
AARONSON, SA .
SCIENCE, 1991, 251 (4989) :72-75