title: START-GAP3/DLC3 is a GAP for RhoA and Cdc42 and is localized in focal adhesions regulating cell morphology.
abstract: In the human genome there are three genes encoding RhoGAPs that contain the START (steroidogenic acute regulatory protein (StAR)-related lipid transfer)-domain. START-GAP3/DLC3 is a tumor suppressor gene similar to two other human START-GAPs known as DLC1 or DLC2. Although expression of START-GAP3/DLC3 inhibits the proliferation of cancer cells, its molecular function is not well understood. In this study we carried out biochemical characterization of START-GAP3/DLC3, and explored the effects of its expression on cell morphology and intracellular localization. We found that START-GAP3/DLC3 serves as a stimulator of PLCdelta1 and as a GAP for both RhoA and Cdc42 in vitro. Moreover, we found that the GAP activity is responsible for morphological changes. The intracellular localization of endogenous START-GAP3/DLC3 was explored by immunocytochemistry and was revealed in focal adhesions. These results indicate that START-GAP3/DLC3 has characteristics similar to other START-GAPs and the START-GAP family seems to share common characteristics.
authors.affiliation: Graduate School of Life Science, University of Hyogo, Harima Science Garden City, Hyogo-ken 678-1297, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Kawai
authors.forename: Minoru
authors.initials: M
authors.lastname: Kiyota
authors.forename: Junichi
authors.initials: J
authors.lastname: Seike
authors.forename: Yuko
authors.initials: Y
authors.lastname: Deki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yagisawa
mesh_terms: D048429:Cell Size; D017630:Connexins / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism* / Q000648:ultrastructure*; D006367:HeLa Cells; D006801:Humans; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D017630:Connexins; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein