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© The Rockefeller University Press, 0021-9525/1999//921 $5.00
The Journal of Cell Biology, Volume 147, Number 5, , 1999 921-928

Brief Report

Human Ect2 Is an Exchange Factor for Rho Gtpases, Phosphorylated in G2/M Phases, and Involved in Cytokinesis



Takashi Tatsumotoa, Xiaozhen Xiea, Rayah Blumenthala, Isamu Okamotoa, and Toru Mikia

a Molecular Tumor Biology Section, Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892-4255
Basic Research Laboratory, National Cancer Institute, Building 37, Room 1E24, 37 Convent Dr., MSC 4255, Bethesda, MD 20892.(301) 496-8479(301) 496-2289

toru{at}helix.nih.gov

Animal cells divide into two daughter cells by the formation of an actomyosin-based contractile ring through a process called cytokinesis. Although many of the structural elements of cytokinesis have been identified, little is known about the signaling pathways and molecular mechanisms underlying this process. Here we show that the human ECT2 is involved in the regulation of cytokinesis. ECT2 catalyzes guanine nucleotide exchange on the small GTPases, RhoA, Rac1, and Cdc42. ECT2 is phosphorylated during G2 and M phases, and phosphorylation is required for its exchange activity. Unlike other known guanine nucleotide exchange factors for Rho GTPases, ECT2 exhibits nuclear localization in interphase, spreads throughout the cytoplasm in prometaphase, and is condensed in the midbody during cytokinesis. Expression of an ECT2 derivative, containing the NH2-terminal domain required for the midbody localization but lacking the COOH-terminal catalytic domain, strongly inhibits cytokinesis. Moreover, microinjection of affinity-purified anti-ECT2 antibody into interphase cells also inhibits cytokinesis. These results suggest that ECT2 is an important link between the cell cycle machinery and Rho signaling pathways involved in the regulation of cell division.

Key Words: cell division • phosphorylation • nucleotide exchange • oncogene • microinjection

© 1999 The Rockefeller University Press

T. Tatsumoto and X. Xie contributed equally to this paper.

Abbreviations used in this paper: BRCT, BRCA1 COOH-terminal repeat; DAPI, 4',6-diamidino-2'-phenylindole; DH, Dbl homology domain; ECT2-C, ECT2 COOH-terminal half; ECT2-F, full-length ECT2; ECT2-N, ECT2 NH2-terminal half; GDP, guanosine diphosphate; GEF, guanine nucleotide exchange factor; GFP, green fluorescent protein.


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