Allosteric protein kinase regulation by pseudokinases: insights from STRAD.
Protein kinases regulate a plethora of diverse cellular functions. Their highly controlled activation is subject to an equally diverse repertoire of regulatory mechanisms. Pseudokinases, a class of proteins that possess a structurally related protein kinase domain that lacks phospho-transfer function, are emerging as critical yet mysterious regulators of other protein kinases. A new structural and functional analysis of the pseudokinase STRAD provides insight into the mechanism by which it allosterically regulates the catalytic function of the protein kinase LKB1 and hints at an evolution from a classical kinase-substrate relationship.
Rajakulendran
Thanashan
T
1Centre for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada.
Sicheri
Frank
F
D000091162:AMP-Activated Protein Kinase Kinases; D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000378:metabolism*; D000494:Allosteric Regulation; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D049490:Systems Biology
D033942:Adaptor Proteins, Vesicular Transport; C540569:CAB39 protein, human; D002135:Calcium-Binding Proteins; C476400:STRADA protein, human; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases