Editors' ChoiceNonreceptor Tyrosine Kinases

Functions for the Pseudokinase Domain

Science's STKE  16 May 2000:
Vol. 2000, Issue 32, pp. tw11
DOI: 10.1126/stke.2000.32.tw11

Jak2 is a nonreceptor tyrosine kinase involved in transducting signals from cytokine receptors. Saharinen et al. demonstrate that the JH2 domain, which is a pseudokinase domain, negatively regulates the activity of Jak2 by transfecting cells with a variety of mutant Jak2 constructs. Deletion of the JH2 domain had several effects: (i) increased tyrosine phosphorylation of Jak, (ii) increased Jak kinase activity, (iii) increased phosphorylation of STAT5 along with loss of dependence on the SH2 domain of STAT5 for phosphorylation, and (iv) activated a STAT reporter gene in a ligand-independent manner. Their data support an intramolecular interaction between the JH1 kinase domain and the JH2 pseudokinase domain that regulates kinase activity and substrate recognition.

Saharinen, P., Takaluoma, K., and Silvennionen, O. (2000) Regulation of the Jak2 tyrosine kinase by its pseudokinase domain. Mol. Cell. Biol. 20: 3387-3395. [Abstract] [Full Text]