Identification of an Autoinhibitory Domain of p21-activated Protein Kinase 5
Copyright policy )Identification of an Autoinhibitory Domain of p21-activated Protein Kinase 5
The p21-activated protein kinases (Paks) are serine/threonine protein kinases activated by binding to Rho family small GTPases, Rac and Cdc42. Recently, Pak family members have been subdivided into two groups, I and II. Group II Paks, including Pak4, Pak5, and Pak6, does not contain the highly conserved autoinhibitory domain that is found in the group I Paks members, i.e. Pak1, Pak2, and Pak3. In the present study, we have purified the glutathione S-transferase fusion form of Pak5 and shown for the first time that Pak5 autophosphorylation can be activated by GTP bound form of Cdc42. Mutation of histidine residues 19 and 22 to leucine on the p21-binding domain of Pak5 completely abolished the binding of Cdc42 and the Cdc42-mediated autophosphorylation. On the other hand, mutation of tyrosine 40 to cysteine of Cdc42 did not knockout the binding of Pak5. Analysis of C-terminal deletion mutants has identified an autoinhibitory fragment of Pak5 that is absent from other group II Pak family members. Taken together, these results suggest that Pak5, like Pak1, contains an autoinhibitory domain and its activity is regulated by Cdc42.
- University of Hong Kong (香港大學) China (People's Republic of)
- University of Hong Kong China (People's Republic of)
Protein Structure, Recombinant Fusion Proteins - metabolism, 572, Recombinant Fusion Proteins, Molecular Sequence Data, Sequence Homology, Protein Serine-Threonine Kinases, Transfection, Biochemistry, Plasmids - metabolism, Cell Line, Leucine, Guanosine Triphosphate - metabolism, Humans, Histidine, Amino Acid Sequence, Phosphorylation, cdc42 GTP-Binding Protein, Biology, Protein-Serine-Threonine Kinases - metabolism, Glutathione Transferase, Sequence Homology, Amino Acid, Leucine - chemistry, Histidine - chemistry, cdc42 GTP-Binding Protein - metabolism, Protein Structure, Tertiary, Amino Acid, Tyrosine - chemistry, p21-Activated Kinases, Mutation, Glutathione Transferase - metabolism, Tyrosine, Guanosine Triphosphate, Tertiary, Gene Deletion, Plasmids, Protein Binding
Protein Structure, Recombinant Fusion Proteins - metabolism, 572, Recombinant Fusion Proteins, Molecular Sequence Data, Sequence Homology, Protein Serine-Threonine Kinases, Transfection, Biochemistry, Plasmids - metabolism, Cell Line, Leucine, Guanosine Triphosphate - metabolism, Humans, Histidine, Amino Acid Sequence, Phosphorylation, cdc42 GTP-Binding Protein, Biology, Protein-Serine-Threonine Kinases - metabolism, Glutathione Transferase, Sequence Homology, Amino Acid, Leucine - chemistry, Histidine - chemistry, cdc42 GTP-Binding Protein - metabolism, Protein Structure, Tertiary, Amino Acid, Tyrosine - chemistry, p21-Activated Kinases, Mutation, Glutathione Transferase - metabolism, Tyrosine, Guanosine Triphosphate, Tertiary, Gene Deletion, Plasmids, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).68 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average
Citations provided by BIP!Popularity provided by BIP!