Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis

Animal cells divide into two daughter cells by the formation of an actomyos in-based contractile ring through a process called cytokinesis. Although ma ny of the structural elements of cytokinesis have been identified, little i s known about the signaling pathways and molecular mechanisms underlying th is process. Here we show that the human ECT2 is involved in the regulation of cytokinesis. ECT2 catalyzes guanine nucleotide exchange on the small GTP ases, RhoA, Rad, and Cdc42. ECT2 is phosphorylated during G2 and M phases, and phosphorylation is required for its exchange activity. Unlike other kno wn guanine nucleotide exchange factors for Rho GTPases, ECT2 exhibits nucle ar localization in interphase, spreads through-out the cytoplasm in prometa phase, and is condensed in the midbody during cytokinesis. Expression of an ECT2 derivative, containing the NH2-terminal domain required for the midbo dy localization but lacking the COOH-terminal catalytic domain, strongly in hibits cytokinesis, Moreover, microinjection of affinity-purified anti-ECT2 antibody into interphase cells also inhibits cytokinesis, These results su ggest that ECT2 is an important link between the cell cycle machinery and R ho signaling pathways involved in the regulation of cell division.