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Akt phosphorylation of serine 21 on Pak1 modulates Nck binding and cell migration

Guo-Lei Zhou1, Ya Zhuo, Charles C King

  • 1Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Molecular and Cellular Biology
|October 31, 2003
PubMed

Insights

Akt signaling modulates cell migration by regulating the interaction between p21-activated kinases (Paks) and the Nck adaptor protein. This phosphorylation event at serine 21 influences cell movement.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Biochemistry

Background:

  • p21-activated kinases (Paks) are crucial regulators of cell functions, activated by GTPases and kinases.
  • Akt and PDK-1 are known activators of Paks, influencing downstream signaling pathways.

Purpose of the Study:

  • To investigate the role of Akt in Pak1 activation and its downstream effects.
  • To elucidate the mechanism by which Akt influences Pak1 activity and its interaction with adaptor proteins.

Main Methods:

  • In vitro kinase assays using Akt and Pak1.
  • Phosphorylation site mapping on Pak1.
  • Co-expression studies in HeLa cells.
  • Peptide-based assays to disrupt Nck/Pak binding.
  • Cell migration assays.

Main Results:

  • Akt directly phosphorylates Pak1 at serine 21, enhancing its activation.
  • Phosphorylation of serine 21 by Akt reduces the binding of the Nck adaptor protein to Pak1.
  • Akt-mediated release of Pak1 from focal adhesions in HeLa cells.
  • Disruption of Nck/Pak binding inhibits Akt-stimulated cell migration.

Conclusions:

  • Akt signaling regulates cell migration by modulating the Nck-Pak interaction through phosphorylation of Pak1 at serine 21.
  • This mechanism highlights a novel pathway for Akt in controlling cell motility.

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