Emerging roles of pseudokinases.
Kinases control virtually all aspects of biology. Forty-eight human proteins have a kinase-like domain that lacks at least one of the conserved catalytic residues; these proteins are therefore predicted to be inactive and have been termed pseudokinases. Here, we describe exciting work suggesting that pseudokinases, despite lacking the ability to phosphorylate substrates, are still pivotal in regulating diverse cellular processes. We review evidence that the pseudokinase STRAD controls the function of the tumour suppressor kinase LKB1 and that a single amino acid substitution within the pseudokinase domain of the tyrosine kinase JAK2 leads to several malignant myeloproliferative disorders. We also discuss the emerging functions of other pseudokinases, including HER3 (also called ErbB3), EphB6, CCK4 (also called PTK7), KSR, Trb3, GCN2, TRRAP, ILK and CASK.
Boudeau
Jérôme
J
MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH , UK.
Miranda-Saavedra
Diego
D
Barton
Geoffrey J
GJ
Alessi
Dario R
DR
D000091162:AMP-Activated Protein Kinase Kinases; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D053614:Janus Kinase 2; D051379:Mice; D009154:Mutation / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
D033942:Adaptor Proteins, Vesicular Transport; D011518:Proto-Oncogene Proteins; C476400:STRADA protein, human; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases