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 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 NH(2)-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.
Tatsumoto
T
T
Molecular Tumor Biology Section, Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
Xie
X
X
Blumenthal
R
R
Okamoto
I
I
Miki
T
T
D000906:Antibodies / Q000494:pharmacology; D000918:Antibody Specificity; D002455:Cell Division / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D016195:G2 Phase / Q000502:physiology*; D006131:Growth Inhibitors / Q000096:biosynthesis; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D008845:Microinjections; D008938:Mitosis / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000906:Antibodies; C489850:ECT2 protein, human; D006131:Growth Inhibitors; D020662:Guanine Nucleotide Exchange Factors; D011518:Proto-Oncogene Proteins; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins