Doctor of Philosophy (PhD)
Biochemistry & Molecular Biology
Dr. Paul L. Sorgen
Phosphorylation of Cx43 is a process that regulates various functionalities of the gap junction including assembly, stability, internalization, turnover, channel permeability and channel gating. Src has been shown to phosphorylate Cx43 at Y247, Y265, Y313 and regulate gap junctions. Intercellular communication in B and T cells is necessary to mediate adaptive immune response. However, there is little-to-no expression of Src in these lymphocytes. An in vitro kinase screen identified Bruton’s tyrosine kinase (BTK) and Interleukin 2-inducible T-cell kinase (ITK) to phosphorylate Cx43. Mass spectrometry identified Tyr residues to be phosphorylated by BTK and ITK, and these residues are similar to the ones phosphorylated by Src. Overexpression of BTK or ITK in HEK293T cells caused increased phosphorylation of Y247 along with decreased gap junctional intercellular communication (GJIC), without changing the cellular localization of Cx43. Similar results were observed with experiments in B and T lymphocytes as well. Our study indicates BTK and ITK to play a role in Cx43 phosphorylation-mediated regulation of gap junctional intercellular communication.
Basu, Ishika, "Gap Junctional Intercellular Communication: Role of Cx43 Phosphorylation by Tyrosine Kinases" (2023). Theses & Dissertations. 751.