Vihinen M, Nore B F, Mattsson P T, Bäckesjö C M, Nars M, Koutaniemi S, Watanabe C, Lester T, Jones A, Ochs H D, Smith C I
Department of Biosciences, University of Helsinki, Finland.
FEBS Lett. 1997 Aug 18;413(2):205-10. doi: 10.1016/s0014-5793(97)00912-5.
Tec family protein tyrosine kinases have in their N-terminus two domains. The PH domain is followed by Tec homology (TH) domain, which consists of two motifs. The first pattern, Btk motif, is also present in some Ras GAP molecules. C-terminal half of the TH domain, a proline-rich region, has been shown to bind to SH3 domains. Mutations in Bruton's tyrosine kinase (Btk) belonging to the Tec family cause X-linked agammaglobulinemia (XLA) due to developmental arrest of B cells. Here we present the first missense mutations in the TH domain. The substitutions affect a conserved pair of cysteines, residues 154 and 155, involved in Zn2+ binding and thereby the mutations alter protein folding and stability.
Tec家族蛋白酪氨酸激酶在其N端有两个结构域。PH结构域之后是Tec同源性（TH）结构域，该结构域由两个基序组成。第一个模式，即Btk基序，也存在于一些Ras GAP分子中。TH结构域的C端一半是富含脯氨酸的区域，已被证明可与SH3结构域结合。属于Tec家族的布鲁顿酪氨酸激酶（Btk）中的突变会导致B细胞发育停滞，从而引起X连锁无丙种球蛋白血症（XLA）。在此，我们展示了TH结构域中的首个错义突变。这些替换影响了参与锌离子结合的一对保守半胱氨酸残基，即154和155位残基，从而这些突变改变了蛋白质的折叠和稳定性。
