Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase Pin1.

Article Details


Yu L, Mohamed AJ, Vargas L, Berglof A, Finn G, Lu KP, Smith CI

Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase Pin1.

J Biol Chem. 2006 Jun 30;281(26):18201-7. Epub 2006 Apr 27.

PubMed ID
16644721 [ View in PubMed

Bruton tyrosine kinase (Btk) is expressed in B-lymphocytes. Mutations in Btk cause X-linked agammaglobulinemia in humans. However, the mechanism of activation and signaling of this enzyme has not been fully investigated. We have here shown that the peptidylprolyl cis/trans isomerase (PPIase) Pin1 is a negative regulator of Btk, controlling its expression level by reducing its half-life, whereas the catalytic activity of Btk was unaffected. The negative regulatory effect of Pin1 was observed both in cell lines and in Pin(-/-) mice and was found to be dependent on a functionally intact Btk. This may constitute a feedback loop for the regulation of Btk. The target region in Btk was localized to the pleckstrin homology domain suggesting that interphase phosphorylation of serine 115 (Ser-115) in Btk is required, whereas mitosis phosphorylation of serine 21 (Ser-21) is critical. Accordingly, Pin 1 was shown to associate with Btk through binding to Ser-21 and -115, respectively, both of which lie in a classical Pin1-binding pocket. Using a phosphomitotic antibody, it was found that Btk harbors a bona fide MPM2 epitope corresponding to a phosphorylated serine or threonine residue followed by a proline. Our results indicate that the peptidylprolyl isomerase Pin1 interacts with Btk in a cell cycle-dependent manner, regulating the Btk expression level.

DrugBank Data that Cites this Article

NameUniProt ID
Tyrosine-protein kinase BTKQ06187Details
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1Q13526Details