title: Interaction between PAK and nck: a template for Nck targets and role of PAK autophosphorylation.
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.
authors.affiliation: Glaxo-IMCB Group, Institute of Molecular & Cell Biology, Singapore 117609, Singapore.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Zhao
authors.forename: E
authors.initials: E
authors.lastname: Manser
authors.forename: L
authors.initials: L
authors.lastname: Lim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019943:Amino Acid Substitution; D006801:Humans; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D054462:p21-Activated Kinases; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C078332:Nck protein; D015513:Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases