The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome

Nat Cell Biol. 2005 Oct;7(10):937-46. doi: 10.1038/ncb1309. Epub 2005 Sep 25.

Abstract

Although HEF1 has a well-defined role in integrin-dependent attachment signalling at focal adhesions, it relocalizes to the spindle asters at mitosis. We report here that overexpression of HEF1 causes an increase in centrosome numbers and multipolar spindles, resembling defects induced by manipulation of the mitotic regulatory kinase Aurora-A (AurA). We show that HEF1 associates with and controls activation of AurA. We also show that HEF1 depletion causes centrosomal splitting, mono-astral spindles and hyperactivation of Nek2, implying additional action earlier in the cell cycle. These results provide new insight into the role of an adhesion protein in coordination of cell attachment and division.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Aurora Kinases
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Centrosome / metabolism*
  • Enzyme Activation / physiology
  • Focal Adhesions / physiology
  • HeLa Cells
  • Humans
  • NIMA-Related Kinases
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Spindle Apparatus / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • NEDD9 protein, human
  • Phosphoproteins
  • Aurora Kinases
  • NEK2 protein, human
  • NIMA-Related Kinases
  • Protein-Serine-Threonine Kinases