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.
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Lu, BW
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Ackerman, L
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机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Ackerman, L
;
Jan, LY
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机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Jan, LY
;
Jan, YN
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Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Lu, BW
;
Ackerman, L
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机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Ackerman, L
;
Jan, LY
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机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Jan, LY
;
Jan, YN
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Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA