1 research outputs found
Tumor suppressor function of Bruton tyrosine kinase is independent of its catalytic activity
During B-cell development in the mouse, Bruton tyrosine kinase (Btk) and
the adaptor protein SLP-65 (Src homology 2 [SH2] domain-containing
leukocyte protein of 65 kDa) limit the expansion and promote the
differentiation of pre-B cells. Btk is thought to mainly function by
phosphorylating phospholipase Cgamma2, which is brought into close
proximity of Btk by SLP-65. However, this model was recently challenged by
the identification of a role for Btk as a tumor suppressor in the absence
of SLP-65 and by the finding that Btk function is partially independent of
its kinase activity. To investigate if enzymatic activity is critical for
the tumor suppressor function of Btk, we crossed transgenic mice
expressing the kinase-inactive K430R-Btk mutant onto a Btk/SLP-65
double-deficient background. We found that K430R-Btk expression rescued
the severe developmental arrest at the pre-B-cell stage in Btk/SLP-65
double-deficient mice. Moreover, K430R-Btk co