<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">KOKABEE, MOSTAFA</style></author><author><style face="normal" font="default" size="100%">WANG, XIANHUI</style></author><author><style face="normal" font="default" size="100%">VOORAND, ELENA</style></author><author><style face="normal" font="default" size="100%">ALIN, EDEN</style></author><author><style face="normal" font="default" size="100%">KOKABEE, LEILA</style></author><author><style face="normal" font="default" size="100%">KHAN, FAIZA</style></author><author><style face="normal" font="default" size="100%">DESROSIERS, SOPHIA</style></author><author><style face="normal" font="default" size="100%">CONKLIN, DOUGLAS S.</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">Palmitoylation of the Alternative Amino Terminus of the BTK-C Isoform Controls Subcellular Distribution and Signaling</style></title><secondary-title><style face="normal" font="default" size="100%">Cancer Genomics - Proteomics</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2022</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2022-07-01 00:00:00</style></date></pub-dates></dates><pages><style  face="normal" font="default" size="100%">415-427</style></pages><doi><style  face="normal" font="default" size="100%">10.21873/cgp.20329</style></doi><volume><style face="normal" font="default" size="100%">19</style></volume><issue><style face="normal" font="default" size="100%">4</style></issue><abstract><style  face="normal" font="default" size="100%">Background: The alternative transcriptional isoform of Bruton’s tyrosine kinase, BTK-C, is expressed in a wide variety of epithelial tumor types where it impacts apoptosis resistance, therapeutic escape, and glucose uptake. The initial exon in BTK-C encodes a 34 amino acid extension of the amino terminus of the canonical BTK-A isoform. Its function is unknown. Materials and Methods: Site-directed mutagenesis, acylation assays and expression studies in cancer cell lines were used to determine the effects that the BTK-C first exon sequence has on kinase activity, subcellular localization and cell physiology. Analysis of BTK-C expression in tumors was conducted using genomic databases. Results: BTK-C is palmitoylated on two cysteine residues. BTK-C localization at the plasma membrane is dependent upon phosphatidylinositol 3,4,5-triphosphate (PIP3) levels as well as palmitoylation. In epithelial cancer cells, both BTK-A and BTK-C isoforms are recruited to the plasma membrane; however, BTK-A also localizes to the nucleus whereas BTK-C has a primarily perinuclear distribution. Transcription of the BTK-C isoform is inversely correlated with expression of commonly activated breast cancer signaling receptors in breast tumors. In MDA-MB-231 cells, BTK-C expression confers modest increases in proliferation and glucose uptake rates compared to BTK-A. Conclusion: Palmitoylation affects localization and regulation of BTK-C in epithelial tumor cells where it functions as an important survival factor. Expression of either palmitoylated or non-palmitoylated kinase isoforms that function in PI3K signaling may be a common regulatory feature as nine other soluble kinases in the human genome possess similarly encoded alternative N-termini (ANT).</style></abstract></record></records></xml>