Boudeau Jérôme, Miranda-Saavedra Diego, Barton Geoffrey J, Alessi Dario R
MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH , UK.
Trends Cell Biol. 2006 Sep;16(9):443-52. doi: 10.1016/j.tcb.2006.07.003. Epub 2006 Aug 1.
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.
激酶几乎控制着生物学的所有方面。48种人类蛋白质具有激酶样结构域，但至少缺少一个保守的催化残基；因此，这些蛋白质预计是无活性的，被称为假激酶。在此，我们描述了一项令人兴奋的研究工作，表明假激酶尽管缺乏磷酸化底物的能力，但在调节多种细胞过程中仍然至关重要。我们综述了相关证据，即假激酶STRAD控制肿瘤抑制激酶LKB1的功能，以及酪氨酸激酶JAK2的假激酶结构域内的单个氨基酸取代会导致几种恶性骨髓增殖性疾病。我们还讨论了其他假激酶的新功能，包括HER3（也称为ErbB3）、EphB6、CCK4（也称为PTK7）、KSR、Trb3、GCN2、TRRAP、ILK和CASK。
