| First Author | Swanson KD | Year | 2008 |
| Journal | Mol Cell | Volume | 32 |
| Issue | 4 | Pages | 564-75 |
| PubMed ID | 19026786 | Mgi Jnum | J:142190 |
| Mgi Id | MGI:3820715 | Doi | 10.1016/j.molcel.2008.09.022 |
| Citation | Swanson KD, et al. (2008) The Skap-hom dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch. Mol Cell 32(4):564-75 |
| abstractText | PH domains, by binding to phosphoinositides, often serve as membrane-targeting modules. Using crystallographic, biochemical, and cell biological approaches, we have uncovered a mechanism that the integrin-signaling adaptor Skap-hom uses to mediate cytoskeletal interactions. Skap-hom is a homodimer containing an N-terminal four-helix bundle dimerization domain, against which its two PH domains pack in a conformation incompatible with phosphoinositide binding. The isolated PH domains bind PI[3,4,5]P(3), and mutations targeting the dimerization domain or the PH domain's PI[3,4,5]P(3)-binding pocket prevent Skap-hom localization to ruffles. Targeting is retained when the PH domain is deleted or by combined mutation of the PI[3,4,5]P(3)-binding pocket and the PH/dimerization domain interface. Thus, the dimerization and PH domain form a PI[3,4,5]P(3)-responsive molecular switch that controls Skap-hom function. |
