FIGURE 2.

(A) Relative expression of Bruton’s tyrosine kinase (BTK)-A and BTK-C transcripts in epithelial tumors and normal tissue. Exon abundance for reads in TCGA Firehouse datasets for prostate adenocarcinoma (PRAD), bladder adenocarcinoma (BLCA), and lung squamous (LUSC) tumors plotted using the TSVdb web application. Each tumor type shows expression of the BTK-C transcript. Significant BTK-A transcription is also observed. (B) BTK isoform signaling. The BTK-A isoform is activated by B-cell receptor signaling involving the LYN and SYK kinases. PI3K activation increases PIP₃ levels, which in turn activate BTK-A to phosphorylate PLCγ2 leading to the nuclear localization and activation of maturation transcriptional programs. In epithelial cancer cells, the key activation of PI3K can occur through diverse receptor protein tyrosine kinases, G-protein-coupled receptors, and other types of receptors, making BTK-C an important signaling node in these cells. Activation also involves SRC family kinases (Sfk). The downstream effectors of BTK-C are not completely understood at present, although the protein was isolated as a critical determinant of epithelial cancer cell survival. p65BTK (not shown) does not contain a complete PH domain and may be activated by other mechanisms.