How Do Protein Kinases Take a Selfie (Autophosphorylate)?
Eukaryotic protein kinases (EPKs) control most biological processes and play central roles in many human diseases. To become catalytically active, EPKs undergo conversion from an inactive to an active conformation, an event that depends upon phosphorylation of their activation loop. Intriguingly, EPKs can use their own catalytic activity to achieve this critical phosphorylation. In other words, paradoxically, EPKs catalyze autophosphorylation when supposedly in their inactive state. This indicates the existence of another important conformation that specifically permits autophosphorylation at the activation loop, which in turn imposes adoption of the active conformation. This can be considered a prone-to-autophosphorylate conformation. Recent findings suggest that in prone-to-autophosphorylate conformations catalytic motifs are aligned allosterically, by dimerization or by regulators, and support autophosphorylation in cis or trans.
Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Jonah
J
Beenstock
Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel; Department of Microbiology, Yong loo lin School of Medicine, National University of Singapore, Singapore, Singapore.
Navit
N
Mooshayef
Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel; CREATE-NUS-HUJ Cellular & Molecular Mechanisms of Inflammation Program, National University of Singapore, 1 CREATE WAY, Innovation Wing, Singapore, Singapore; Department of Microbiology, Yong loo lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address: engelber@mail.huji.ac.il.
David
D
Engelberg
D000494:Allosteric Regulation; D000495:Allosteric Site; D020816:Amino Acid Motifs; D055162:Biocatalysis; D020134:Catalytic Domain; D015870:Gene Expression; D006801:Humans; D010766:Phosphorylation; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D020543:Proteome / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D020543:Proteome; D011494:Protein Kinases
allostery; autophosphorylation; dimerization; protein kinase.