Interaction between PAK and nck: a template for Nck targets and role of PAK autophosphorylation

Mol Cell Biol. 2000 Jun;20(11):3906-17. doi: 10.1128/MCB.20.11.3906-3917.2000.

Abstract

The kinase PAK binds tightly to the SH3 domain of its partner PIX via a central proline-rich sequence. A different N-terminal sequence allows alphaPAK to bind an SH3 domain of the adaptor Nck. The Nck SH3[2] domain interacts equally with an 18-mer PAK-derived peptide and full-length alphaPAK. Detailed analysis of this binding by saturation substitution allows related Nck targets to be accurately identified from sequence characteristics alone. All Nck SH3[2] binding proteins, including PAK, NIK, synaptojanin, PRK2, and WIP, possess the motif PXXPXRXXS; in the case of PAK, serine phosphorylation at this site negatively regulates binding. We show that kinase autophosphorylation blocks binding by both Nck and PIX to alphaPAK, thus providing a mechanism to regulate PAK interactions with its SH3-containing partners. One cellular consequence of the regulatable binding of PAK is facilitation of its cycling between cytosolic and focal complex sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Substitution
  • Humans
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Sequence Analysis, DNA
  • p21-Activated Kinases
  • src Homology Domains*

Substances

  • Adaptor Proteins, Signal Transducing
  • Nck protein
  • Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • p21-Activated Kinases