Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity.

摘要: Previously, the pleiotropic “master kinase” casein kinase 2 (CK2) was shown to interact with CFTR, protein responsible for cystic fibrosis (CF). Moreover, CK2 inhibition abolished CFTR conductance in cell-attached membrane patches, native epithelial ducts, and Xenopus oocytes. possesses two phosphorylation sites (S422 T1471), unclear impact on its processing trafficking. Here, we investigated effects of mutating these abundance, maturation, degradation coupled ion channel activity surface expression. We report that significantly decreased wild-type (wt) no effect F508del CFTR. Eliminating at S422 T1471 revealed antagonistic roles trafficking: activation versus inhibition, as evidenced by a severe trafficking defect T1471D mutant. Notably, mutation Y512, consensus sequence spleen tyrosine (SYK) possibly acting context adjacent common CF-causing F508del, had strong both maturation currents, allowing identification this novel regulator These results reinforce importance residues regulation uncover SYK, recognized controller inflammation.