title: Activation segment exchange: a common mechanism of kinase autophosphorylation?
abstract: The crystal structure of the kinase domain from human checkpoint kinase 2 (Chk2) has shown, for the first time, the reciprocal exchange of activation segments between two adjacent molecules and provides the molecular basis for understanding the observed mode of Chk2 kinase activation via trans-autophosphorylation. With further examples of activation segment exchanged kinase domains now publicly available (i.e. Ste20-like kinase, Ser/Thr kinase 10 and Death-associated protein kinase 3), we suggest that this phenomenon represents a common mechanism of activation amongst a particular subset of protein kinases, that is, those that are dimeric (either transiently or constitutively), that undergo activation by autophosphorylation and that have activation segment amino acid sequences that do not resemble those of their substrate consensus sequence.
authors.affiliation: Cancer Research UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research, Chelsea, London, SW3 6JB, UK. antony.oliver@icr.ac.uk
authors.forename: Antony W
authors.initials: AW
authors.lastname: Oliver
authors.forename: Stefan
authors.initials: S
authors.lastname: Knapp
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Pearl
mesh_terms: D000818:Animals; D064447:Checkpoint Kinase 2; D018360:Crystallography, X-Ray / Q000379:methods; D019281:Dimerization; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D008968:Molecular Conformation; D010766:Phosphorylation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012694:Serine / Q000737:chemistry; D013912:Threonine / Q000737:chemistry
chemical_list: D013912:Threonine; D012694:Serine; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases