AKAP220 Protein Organizes Signaling Elements That Impact Cell Migration*

Background: AKAP220 organizes the signaling enzymes PKA, GSK-3, and phosphoprotein phosphatase PP1. Results: AKAP220 interacts with the scaffolding protein IQGAP1 to assimilate and process calcium and cAMP signals at leading edges of migrating cells. Conclusion: AKAP220/IQGAP1 networks position calcium and cAMP-responsive signaling enzymes near substrates at the +TIPs of growing microtubules. Significance: Anchored kinase/microtubule effector protein networks propagate cell motility. 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.

• Publication year

  2011

• Venue

  Journal of Biological Chemistry

• Publication date

  2011-09-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M111.277756PMID 21890631PMCID 3234751
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β.

  2011cited by this paper
• Anchored Protein Kinase A Recruitment of Active Rac GTPase

  2011cited by this paper
• CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule.

  2010cited by this paper
• Specificity and spatial dynamics of protein kinase A signaling organized by A-kinase-anchoring proteins.

  2010cited by this paper
• ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells

  2010cited by this paper
• IQGAP1 regulation and roles in cancer.

  2009cited by this paper
• GSK3β phosphorylation modulates CLASP–microtubule association and lamella microtubule attachment

  2009cited by this paper
• Phosphorylation of CLASP2 by GSK-3β regulates its interaction with IQGAP1, EB1 and microtubules

  2009cited by this paper
• Cell Signaling in Space and Time: Where Proteins Come Together and When They’re Apart

  2009cited by this paper
• An Adenylyl Cyclase-mAKAPβ Signaling Complex Regulates cAMP Levels in Cardiac Myocytes*

  2009cited by this paper
• mAKAP Compartmentalizes Oxygen-Dependent Control of HIF-1α

  2008cited by this paper
• Role of adenomatous polyposis coli (APC) and microtubules in directional cell migration and neuronal polarization.

  2008cited by this paper
• A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase.

  2006cited by this paper
• IQGAP1 in cellular signaling: bridging the GAP.

  2006cited by this paper
• Role of CLASP2 in microtubule stabilization and the regulation of persistent motility.

  2006cited by this paper
• Molecular basis of AKAP specificity for PKA regulatory subunits.

  2006cited by this paper
• IQGAP1: a key regulator of adhesion and migration

  2005cited by this paper
• CLASP1 and CLASP2 bind to EB1 and regulate microtubule plus-end dynamics at the cell cortex

  2005cited by this paper
• Spatial regulation of CLASP affinity for microtubules by Rac1 and GSK3β in migrating epithelial cells

  2005cited by this paper
• EB1 and EB3 control CLIP dissociation from the ends of growing microtubules.

  2005cited by this paper
• CLIPs and CLASPs and cellular dynamics

  2005cited by this paper
• Quantification of microtubule nucleation, growth and dynamics in wound-edge cells

  2005cited by this paper
• IL-13受体α2降低血吸虫病肉芽肿的炎症反应并延长宿主存活时间[英]/Mentink-Kane MM,Cheever AW，Thompson RW，et al//Proc Natl Acad Sci U S A

  2005cited by this paper
• Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration.

  2004cited by this paper
• Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization.

  2004cited by this paper
• IQGAP1 as signal integrator: Ca2+, calmodulin, Cdc42 and the cytoskeleton

  2003cited by this paper
• A-Kinase Anchoring Protein AKAP220 Binds to Glycogen Synthase Kinase-3β (GSK-3β) and Mediates Protein Kinase A-dependent Inhibition of GSK-3β*

  2002cited by this paper
• A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta.

  2002cited by this paper
• Clasps are CLIP-115 and -170 associating proteins involved in the regional regulation of microtubule dynamics in motile fibroblasts.

  2001cited by this paper
• FEBS Lett

  2000cited by this paper
• Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A.

  2000cited by this paper
• Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells.

  1999cited by this paper
• Association of the type 1 protein phosphatase PP1 with the A-kinase anchoring protein AKAP220.

  1999cited by this paper
• An emerging link between cytoskeletal dynamics and cell adhesion molecules in growth cone guidance.

  1998cited by this paper
• Role of IQGAP1, a target of the small GTPases Cdc42 and Rac1, in regulation of E-cadherin- mediated cell-cell adhesion.

  1998cited by this paper
• Actomyosin-based Retrograde Flow of Microtubules in the Lamella of Migrating Epithelial Cells Influences Microtubule Dynamic Instability and Turnover and Is Associated with Microtubule Breakage and Treadmilling

  1997cited by this paper
• Microtubule Treadmilling in Vivo

  1997cited by this paper
• Cloning and Characterization of a Novel A-kinase Anchoring Protein

  1996cited by this paper
• Platelet-derived Growth Factor Stimulates Protein Kinase A through a Mitogen-activated Protein Kinase-dependent Pathway in Human Arterial Smooth Muscle Cells (*)

  1996cited by this paper
• Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B

  1995cited by this paper
• Association of protein kinase A and protein phosphatase 2B with a common anchoring protein.

  1995cited by this paper
• Interaction of the regulatory subunit (RII) of cAMP-dependent protein kinase with RII-anchoring proteins occurs through an amphipathic helix binding motif.

  1991cited by this paper
• Differential turnover of tyrosinated and detyrosinated microtubules.

  1987cited by this paper
• Dynamic instability of microtubule growth

  1984cited by this paper
• Distinct populations of microtubules: tyrosinated and nontyrosinated alpha tubulin are distributed differently in vivo.

  1984cited by this paper

• Elevated synaptic PKA activity and abnormal striatal dopamine signaling in Akap11 mutant mice, a genetic model of schizophrenia and bipolar disorder

  2025cites this paper
• SYT15B promotes tumor progression through interaction with IQGAP1 to activate the MAPK pathway in lung adenocarcinoma.

  2025cites this paper
• POU4F2/Brn-3b is Essential for Spermatogenesis and its Disruption is Linked to Male Infertility in Mice and Humans

  2025cites this paper
• Transcriptomic and epigenomic consequences of heterozygous loss-of-function mutations in AKAP11, a shared risk gene for bipolar disorder and schizophrenia

  2025cites this paper
• Autophagosomes anchor an AKAP11-dependent regulatory checkpoint that shapes neuronal PKA signaling

  2025cites this paper
• TNF-α drives bladder cancer metastasis via METTL3-mediated m6A modification to promote CLASP2/IQGAP1-dependent cytoskeleton remodeling.

  2025cites this paper
• Transcriptomic and epigenomic consequences of heterozygous loss of function mutations in AKAP11, the first large-effect shared risk gene for bipolar disorder and schizophrenia

  2024cites this paper
• Autophagosomes coordinate an AKAP11-dependent regulatory checkpoint that shapes neuronal PKA signaling

  2024cites this paper
• AKAP2-anchored protein phosphatase 1 controls prostatic neuroendocrine carcinoma cell migration and invasion.

  2023cites this paper
• AKAP79/150 coordinates leptin-induced PKA signaling to regulate KATP channel trafficking in pancreatic β-cells

  2021cites this paper
• Kinase-anchoring proteins in ciliary signal transduction.

  2021cites this paper
• Targeting an anchored phosphatase-deacetylase unit restores renal ciliary homeostasis

  2021cites this paper
• The interplay between IQGAP1 and small GTPases in cancer metastasis.

  2021cites this paper
• AKAP Signaling Islands: Venues for Precision Pharmacology.

  2020cites this paper
• AKAP79/150 coordinates leptin-induced PKA activation to regulate KATP channel trafficking in pancreatic β-cells

  2020cites this paper
• IQGAP1 binds AMPK and is required for maximum AMPK activation

  2020cites this paper
• Drugs that Regulate Local Cell Signaling: AKAP Targeting as a Therapeutic Option.

  2020cites this paper
• Site-specific expression of IQGAP1 in human nephrons

  2019cites this paper
• Isoform-specific GSK3A activity is negatively correlated with human sperm motility

  2019cites this paper
• Exogenous CLASP2 protein treatment enhances wound healing in vitro and in vivo

  2019cites this paper
• A genome-wide single nucleotide polymorphism and copy number variation analysis for number of piglets born alive

  2019cites this paper
• Chapter 6 Regulation of Cell Fate in the Brain by GSK 3

  2018cites this paper
• The A-kinase anchoring protein ( AKAP ) glycogen synthase kinase 3 { beta } interaction protein ( GSKIP ) regulates { beta }-catenin through its interactions with both protein kinase A ( PKA ) and GSK 3 { beta }

  2017cites this paper
• CLASP2 is involved in the EMT and early progression after transurethral resection of the bladder tumor

  2017cites this paper
• University of Southern Denmark Characterization of the CLASP2 Protein Interaction Network Identifies SOGA1 as a Microtubule-Associated Protein Sørensen,

  2017cites this paper
• The CLASP2 Protein Interaction Network in Adipocytes Links CLIP2 to AGAP3, CLASP2 to G2L1, MARK2, and SOGA1, and Identifies SOGA1 as a Microtubule-Associated Protein

  2017cites this paper
• Characterization of the CLASP2 Protein Interaction Network Identifies SOGA1 as a Microtubule-Associated Protein*

  2017cites this paper
• Syddansk Universitet Characterization of the CLASP 2 Protein Interaction Network Identifies SOGA 1 as a Microtubule-Associated Protein

  2017cites this paper
• ERK Signals: Scaffolding Scaffolds?

  2016influential citation
• Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease.

  2016cites this paper
• The A-Kinase Anchoring Protein (AKAP) Glycogen Synthase Kinase 3β Interaction Protein (GSKIP) Regulates β-Catenin through Its Interactions with Both Protein Kinase A (PKA) and GSK3β *

  2016cites this paper
• Compartmentalized signaling in the lung

  2016cites this paper
• A-kinase anchoring proteins: Cyclic AMP compartmentalization in neurodegenerative and obstructive pulmonary diseases

  2016cites this paper
• AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption

  2016influential citation
• Protein Kinase A Opposes the Phosphorylation-dependent Recruitment of Glycogen Synthase Kinase 3β to A-kinase Anchoring Protein 220*

  2015cites this paper
• Cytoskeleton Dynamics in Health and Disease: Role of Molecular Switches and Rheostats

  2015cites this paper
• The AKAP220 signaling complex regulates renal aquaporin-2 localization

  2015influential citation
• The biology of IQGAP proteins: beyond the cytoskeleton

  2015cites this paper
• Role of EPAC in axon determination

  2015cites this paper
• Chapter 5: A-kinase anchoring proteins: Cyclic AMP compartmentalization in neurodegenerative and obstructive pulmonary diseases

  2015cites this paper
• Store-operated Ca²⁺-entry and adenylyl cyclase.

  2015cites this paper
• IQGAP1: insights into the function of a molecular puppeteer.

  2015cites this paper
• IQGAPs choreograph cellular signaling from the membrane to the nucleus.

  2015cites this paper
• Pharmacological targeting of AKAP-directed compartmentalized cAMP signalling.

  2015cites this paper
• Protein Kinase A Opposes the Phosphorylation-Dependent Recruitment of Glycogen Synthase Kinase 3 β to A-Kinase Anchoring Protein 220

  2015cites this paper
• Adenylate cyclase-centred microdomains.

  2014cites this paper
• A‐kinase anchoring proteins: cAMP compartmentalization in neurodegenerative and obstructive pulmonary diseases

  2014cites this paper
• FAM123A Binds Microtubules and Inhibits the Guanine Nucleotide Exchange Factor ARHGEF2 to Decrease Actomyosin Contractility*** in a plus-end direction. Domain interaction experiments

  2013cites this paper
• Redox regulation of type Iα PKA in the heart

  2013cites this paper
• Regulation of Cell Fate in the Brain by GSK3

  2013cites this paper
• IQGAP1 and its binding proteins control diverse biological functions.

  2012cites this paper
• Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension.

  2012cites this paper
• FAM123A Binds to Microtubules and Inhibits the Guanine Nucleotide Exchange Factor ARHGEF2 to Decrease Actomyosin Contractility

  2012cites this paper
• IQGAP1: A Regulator of Intracellular Spacetime Relativity

  2012cites this paper
• Cytoskeleton in Mast Cell Signaling

  2012cites this paper