title: AKAP220 protein organizes signaling elements that impact cell migration.
abstract: Cell movement requires the coordinated reception, integration, and processing of intracellular signals. We have discovered that the protein kinase A anchoring protein AKAP220 interacts with the cytoskeletal scaffolding protein IQGAP1 to influence cell motility. AKAP220/IQGAP1 networks receive and integrate calcium and cAMP second messenger signals and position signaling enzymes near their intended substrates at leading edges of migrating cells. IQGAP1 supports calcium/calmodulin-dependent association of factors that modulate microtubule dynamics. AKAP220 suppresses GSK-3β and positions this kinase to allow recruitment of the plus-end microtubule tracking protein CLASP2. Gene silencing of AKAP220 alters the rate of microtubule polymerization and the lateral tracking of growing microtubules and retards cell migration in metastatic human cancer cells. This reveals an unappreciated role for this anchored kinase/microtubule effector protein network in the propagation of cell motility.
authors: Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington 98195, USA.
authors: Jeremy S
authors: JS
authors: Logue
authors: Jennifer L
authors: JL
authors: Whiting
authors: Brian
authors: B
authors: Tunquist
authors: David B
authors: DB
authors: Sacks
authors: Lorene K
authors: LK
authors: Langeberg
authors: Linda
authors: L
authors: Wordeman
authors: John D
authors: JD
authors: Scott
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D054758:A Kinase Anchor Proteins; C099270:AKAP11 protein, human; C497851:CLASP2 protein, human; D002147:Calmodulin; C101203:IQ motif containing GTPase activating protein 1; D008869:Microtubule-Associated Proteins; D020703:ras GTPase-Activating Proteins; D000242:Cyclic AMP; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D002118:Calcium