p21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor B

Ratna K. Vadlamudi, Christopher J. Barnes, Suresh Rayala, Feng Li, Seetharaman Balasenthil, Stevan Marcus, Holly V. Goodson, Aysegul A. Sahin, Rakesh Kumar

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


p21-activated kinase 1 (Pak1) induces cytoskeleton reorganization in part by regulating microtubule dynamics through an elusive mechanism. Using a yeast two-hybrid screen, we identified tubelin cofactor B (TCoB) (a cofactor in the assembly of the α/β-tubulin heterodimers) as an interacting substrate of Pak1. Pak1 directly phosphorylated TCoB in vitro and in vivo on serines 65 and 128 and colocalized with TCoB on newly polymerized microtubules and on centrosomes. TCoB interacted with the GTPase-binding domain of Pak1 and activated Pak1 in vitro and in vivo. In contrast to wild-type TCoB, an S65A, S128A double mutant and knock-down of the endogenous TCoB or Pak1 reduced microtubule polymerization, suggesting that Pak1 phosphorylation is necessary for normal TCoB function. Overexpression of TCoB dramatically increased the number of γ-tubulin-containing microtubule-organizing centers, a phenotype reminiscent of cells overexpressing Pak1. TCoB was overexpressed and phosphorylated in breast tumors. These findings reveal a novel role for TCoB and Pak1 in regulating microtubule dynamics.

Original languageEnglish (US)
Pages (from-to)3726-3736
Number of pages11
JournalMolecular and cellular biology
Issue number9
StatePublished - May 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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