Transcriptional vs. Protein-Level Regulation of the Src-Family Kinases LynA and LynB
Macrophages are specialized white blood cells with roles in pathogen destruction. One of the key activators and regulators of this pathogen destroying immune response is the Src-family kinase (SFK) Lyn. Lyn exists in macrophages as two splice forms, LynA and LynB. Our lab used CRISPR/Cas9 gene editing to generate isoform-specific LynA knockout (KO) mice and LynBKO mice. Surprisingly, macrophages from both LynAKO and LynBKO mice showed higher levels of the remaining isoform. In addition, the levels of other SFKs expressed in macrophages (Fyn, Fgr, or Hck) did not change, suggesting Lyn may have a unique regulatory mechanism that somehow senses the levels of the two Lyn isoforms. It is already known in part this unique Lyn regulatory mechanism occurs at the protein-level through degradation by the E3 ubiquitin ligase c-Cbl, but unknown if regulation also occurs post transcriptionally. The goal of this study is to compare transcriptional vs. protein-level regulation of LynA and LynB. Because of Lyn’s role in macrophage activation, understanding Lyn’s regulatory mechanism will hopefully contribute to therapies aimed at decreasing inflammatory responses.