title: CIIA functions as a molecular switch for the Rac1-specific GEF activity of SOS1.
abstract: Son of sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the guanosine triphosphatases Rac1 and Ras, which mediate signaling initiated by peptide growth factors. In this paper, we show that CIIA is a new binding partner of SOS1. CIIA promoted the SOS1-Rac1 interaction and inhibited the SOS1-Ras interaction. Furthermore, CIIA promoted the formation of an SOS1-EPS8 complex and SOS1-mediated Rac1 activation, whereas it inhibited SOS1-mediated activation of Ras. Transforming growth factor β (TGF-β) up-regulated the expression of CIIA and thereby promoted the association between CIIA and SOS1 in A549 human lung adenocarcinoma cells. Depletion of CIIA in these cells by ribonucleic acid interference inhibited the TGF-β-induced interaction between SOS1 and EPS8, activation of Rac1, and cell migration. Together, these results suggest that CIIA mediates the TGF-β-induced activation of SOS1-Rac1 signaling and cell migration in A549 cells. They further show that CIIA functions as a molecular switch for the GEF activity of SOS1, directing this activity toward Rac1.
authors: Laboratory of Cell Death and Human Diseases, School of Life Sciences, Korea University, Seoul 136-701, South Korea.
authors: Hyun Sub
authors: HS
authors: Hwang
authors: Sang Gil
authors: SG
authors: Hwang
authors: Jun-Ho
authors: JH
authors: Cho
authors: Ji Soo
authors: JS
authors: Chae
authors: Kyoung Wan
authors: KW
authors: Yoon
authors: Ssang-Goo
authors: SG
authors: Cho
authors: Eui-Ju
authors: EJ
authors: Choi
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D004285:Dogs; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D020837:SOS1 Protein / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
chemical_list: C569202:CIIA protein, mouse; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D020837:SOS1 Protein; D016212:Transforming Growth Factor beta; D020830:rac1 GTP-Binding Protein; D018631:ras Proteins