title: Interaction of smoothened with integrin-linked kinase in primary cilia mediates Hedgehog signalling.
abstract: Here we report that ILK localizes in the mouse primary cilium, a sensory organelle required for signalling by the Hedgehog (Hh) pathway. Genetic or pharmacological inhibition of ILK blocks ciliary accumulation of the Hh pathway effector smoothened (Smo) and suppresses the induction of Gli transcription factor mRNAs by SHh. Conditional deletion of ILK or Smo also inhibits SHh-driven activation of Gli2 in the embryonic mouse cerebellum. ILK regulation of Hh signalling probably requires the physical interaction of ILK and Smo in the cilium, and we also show selective cilia-associated interaction of ILK with β-arrestin, a known mediator of Smo-dependent signalling.
authors.affiliation: Centre for Cancer Research.
authors.forename: Badia
authors.initials: B
authors.lastname: Barakat
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.forename: Camden
authors.initials: C
authors.lastname: Lo
authors.forename: Duc
authors.initials: D
authors.lastname: Vu
authors.forename: Elisabetta
authors.initials: E
authors.lastname: De Luca
authors.forename: Jason E
authors.initials: JE
authors.lastname: Cain
authors.forename: Luciano G
authors.initials: LG
authors.lastname: Martelotto
authors.forename: Luciano G
authors.initials: LG
authors.lastname: Martellotto
authors.forename: Shoukat
authors.initials: S
authors.lastname: Dedhar
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Sadler
authors.forename: Die
authors.initials: D
authors.lastname: Wang
authors.forename: D Neil
authors.initials: DN
authors.lastname: Watkins
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Hannigan
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism; D002460:Cell Line; D002531:Cerebellum / Q000196:embryology / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000072086:Smoothened Receptor; D000075746:Zinc Finger Protein Gli2; D000099200:Scaffold Protein ILK
chemical_list: D019390:Arrestins; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D000075746:Zinc Finger Protein Gli2; D000099200:Scaffold Protein ILK; C000618551:Gli2 protein, mouse; C491022:Smo protein, mouse