Exploring the mechanism accounting for Kv1.3-STAT3 interaction and consequent alterations of cancer-relevant pathways

Kv1.3, a member of the Shaker Kv1 channel family, has wide expression in excitable and non-excitable cells and it is involved in different physiological processes. Aberrant expression of Kv1.3 has also been correlated to many pathological states, among them in cancer. In this context, other than ion flux regulation, cytoplasmic N and C-terminal domains participate in cellular signaling through protein-protein interactions. Recently, STAT3 transcription factor was discovered as one of the proteins that interact with Kv1.3. STAT3 is part of an important intracellular pathway, leading to regulation of gene transcription. STAT3 activation has been discovered in majority of human tumor tissues and malignant cell lines. STAT3 harbors Src homology 2 (SH2) domain that potentially binds to the SH2 recognition site of the channel causing their stabilization and activation. Therefore, we investigated this aspect performing experiments that involved generation of Kv1.3 SH2 binding domain mutant channels and addressed whether this mutation disrupt the potential interaction between the channel and STAT3 and prevents STAT3 stabilization.