2. Academic Validation
  3. AAK1-mediated phosphorylation of PDLIM5 and Talin1 promotes focal adhesion disassembly to accelerate cell migration

AAK1-mediated phosphorylation of PDLIM5 and Talin1 promotes focal adhesion disassembly to accelerate cell migration

  • Nat Commun. 2026 May 4. doi: 10.1038/s41467-026-72501-w.
Daniela Krocianova # 1,  Alexander D Dagg # 2,  Rory A Clayton 2,  David Potesil 3,  Veronika Fedorova 1,  Adam Harmanec 1 4 5,  Viktoria Benova 6,  Veronika Bosakova 7,  Jonathan G G Kaufman 2,  Petra Martinkova 3,  Miroslava Alblova 8,  Bernard T Kelly 2,  Katerina Hanakova 3,  Pavel Roudnicky 3,  Stephanie J Spielman 9,  Jan Fric 7 10,  Filip Sroubek 4,  Josef Houser 3 11,  Antoni G Wrobel 12 13,  Evzen Boura 6,  David J Owen 2,  Zbynek Zdrahal 3,  Zuzana Kadlecova 14 15
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
  • 2 Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, UK.
  • 3 CEITEC, Masaryk University, Brno, Czech Republic.
  • 4 Czech Academy of Sciences, Institute of Information Theory and Automation, Prague, Czech Republic.
  • 5 Faculty of Mathematics and Physics, Charles University, Prague, Czech Republic.
  • 6 Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
  • 7 International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic.
  • 8 Centre of Molecular Structure, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Czech Republic.
  • 9 Childhood Cancer Data Lab, Alex's Lemonade Stand Foundation, Bala Cynwyd, PA, USA.
  • 10 Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
  • 11 Core Facility Biomolecular Interactions and Crystallization, Masaryk University, Brno, Czech Republic.
  • 12 Department of Biochemistry, University of Oxford, Oxford, UK.
  • 13 Structural Biology of Disease Processes Laboratory, The Francis Crick Institute, London, UK.
  • 14 Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. [email protected].
  • 15 Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, UK. [email protected].
  • # Contributed equally.
PMID: 42082516 DOI: 10.1038/s41467-026-72501-w
Abstract

AAK1 and BMP2K are serine/threonine kinases traditionally known for phosphorylating AP2 during clathrin-mediated endocytosis (CME), but their broader roles remained incompletely defined. Here, using motif-guided in silico, biochemical, and phosphoproteomic screens, we identify PDLIM5 and Talin1 as direct AAK1/BMP2K substrates. Despite high kinase-domain similarity, only AAK1 promotes cell migration and potentiates focal adhesion (FA) turnover. Live-cell imaging shows that AAK1 recruitment to FAs peaks as disassembly begins. The conserved AAK1 C-terminal PDZ-binding motif mediates direct, low-affinity binding to PDLIM5, providing a plausible mechanism for localized substrate access. Dynamic analyses of phospho-mimetic and phospho-null mutants support a model in which AAK1-dependent phosphorylation promotes timely release of PDLIM5 and Talin1 during FA disassembly. These findings reveal a kinase-driven contribution to FA turnover distinct from protease- and phosphatase-based mechanisms and suggest that functional divergence between AAK1 and BMP2K may provide a strategy to modulate cell migration with reduced impact on CME.

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