BACKGROUND: Mammalian integrin-linked kinase (ILK) was identified in a yeast two-hybrid screen for proteins binding the integrin beta(1) subunit cytoplasmic domain. ILK has been implicated in integrin-mediated signaling and is also an adaptor within integrin-associated cytoskeletal complexes. RESULTS: We identified the C. elegans pat-4 gene in previous genetic screens for mutants unable to assemble integrin-mediated muscle cell attachments. Here, we report that pat-4 encodes the sole C. elegans homolog of ILK. In pat-4 null mutants, embryonic muscle cells form integrin foci, but the subsequent recruitment of vinculin and UNC-89 as well as actin and myosin filaments to these in vivo focal adhesion analogs is blocked. Conversely, PAT-4/ILK requires the ECM component UNC-52/perlecan, the transmembrane protein integrin, and the novel cytoplasmic attachment protein UNC-112 to be properly recruited to nascent attachments. Transgenically expressed "kinase-dead" ILK fully rescues pat-4 loss-of-function mutants. We also identify UNC-112 as a new binding partner for ILK. CONCLUSIONS: Our data strengthens the emerging view that ILK functions primarily as an adaptor protein within integrin adhesion complexes and identifies UNC-112 as a new ILK binding partner.
BACKGROUND:Mammalianintegrin-linked kinase (ILK) was identified in a yeast two-hybrid screen for proteins binding the integrin beta(1) subunit cytoplasmic domain. ILK has been implicated in integrin-mediated signaling and is also an adaptor within integrin-associated cytoskeletal complexes. RESULTS: We identified the C. eleganspat-4 gene in previous genetic screens for mutants unable to assemble integrin-mediated muscle cell attachments. Here, we report that pat-4 encodes the sole C. elegans homolog of ILK. In pat-4 null mutants, embryonic muscle cells form integrin foci, but the subsequent recruitment of vinculin and UNC-89 as well as actin and myosin filaments to these in vivo focal adhesion analogs is blocked. Conversely, PAT-4/ILK requires the ECM component UNC-52/perlecan, the transmembrane protein integrin, and the novel cytoplasmic attachment protein UNC-112 to be properly recruited to nascent attachments. Transgenically expressed "kinase-dead" ILK fully rescues pat-4 loss-of-function mutants. We also identify UNC-112 as a new binding partner for ILK. CONCLUSIONS: Our data strengthens the emerging view that ILK functions primarily as an adaptor protein within integrin adhesion complexes and identifies UNC-112 as a new ILK binding partner.
Authors: Dawn H Siegel; Gabrielle H S Ashton; Homero G Penagos; James V Lee; Heidi S Feiler; Kirk C Wilhelmsen; Andrew P South; Frances J D Smith; Alan R Prescott; Vesarat Wessagowit; Noritaka Oyama; Masashi Akiyama; Daifullah Al Aboud; Khalid Al Aboud; Ahmad Al Githami; Khalid Al Hawsawi; Abla Al Ismaily; Raouf Al-Suwaid; David J Atherton; Ruggero Caputo; Jo-David Fine; Ilona J Frieden; Elaine Fuchs; Richard M Haber; Takashi Harada; Yasuo Kitajima; Susan B Mallory; Hideoki Ogawa; Sedef Sahin; Hiroshi Shimizu; Yasushi Suga; Gianluca Tadini; Kikuo Tsuchiya; Colin B Wiebe; Fenella Wojnarowska; Adel B Zaghloul; Takahiro Hamada; Rajeev Mallipeddi; Robin A J Eady; W H Irwin McLean; John A McGrath; Ervin H Epstein Journal: Am J Hum Genet Date: 2003-06-03 Impact factor: 11.025
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Authors: Brian P Chiswell; Amy L Stiegler; Ziba Razinia; Elina Nalibotski; Titus J Boggon; David A Calderwood Journal: J Struct Biol Date: 2009-12-04 Impact factor: 2.867