PH domain-mediated membrane targeting of Asef.
The APC-associated guanine nucleotide exchange factor (GEF) Asef regulates cell morphology and migration. Asef contains a pleckstrin homology (PH) domain in addition to Dbl homology (DH), APC-binding (ABR), and Src homology 3 (SH3) domains. Here we show that the PH domain of Asef binds to phosphatidylinositol 3,4,5-trisphophate [PtdIns(3,4,5)P3] and targets Asef to the cell-cell adhesion sites in MDCK II cells. Furthermore, we demonstrate that overexpression of Asef in MDCK II cells results in increases in the amounts of E-cadherin and the actin filaments at the sites of cell-cell contact. These results suggest that Asef is targeted via its PH domain to the cell-cell adhesion sites and is involved in the regulation of cell adhesion.
Muroya
Ken
K
Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Kawasaki
Yoshihiro
Y
Hayashi
Tomoatsu
T
Ohwada
Susumu
S
Akiyama
Tetsu
T
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004285:Dogs; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007668:Kidney; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D014162:Transfection
D020662:Guanine Nucleotide Exchange Factors; D010743:Phospholipids; D011994:Recombinant Proteins; D064067:Rho Guanine Nucleotide Exchange Factors