PTK6/BRK (D4O2D) Rabbit Monoclonal Antibody #55174

PTK6/BRK (protein-tyrosine kinase 6, Breast Tumor Kinase) is a non-receptor tyrosine kinase that is closely related to the FRK family of kinases and distantly related to SRC family kinases (1). PTK6/BRK possesses an N-terminal SRC homology 3 (SH3) domain that regulates kinase-substrate interactions, an auto-inhibitory SRC homology 2 (SH2) domain, and a carboxy-terminal kinase domain. Phosphorylation at Tyr342 in the activation loop of the kinase domain upregulates kinase activity, whereas phosphorylation at Tyr447 inhibits kinase activity (2). PTK6/BRK is expressed in differentiated epithelial cells in normal skin, gastrointestinal tract and colon, and its expression level is reportedly upregulated in some cancer cell types, including breast carcinoma, prostate cancer and colon cancer (3-5). Although typically localized in the nucleus of normal cells, PTK6/BRK has also been observed in the cytosol and plasma membrane in some contexts, notably during tumor progression, where it likely interacts with unique substrates. In the nucleus, PTK6/BRK functions to mediate signaling events important for differentiation and apoptosis (4); outside the nucleus, PTK6/BRK may function to relay upstream RTK signaling to downstream pathways via phosphorylation and activation of substrates such as paxillin, STAT and AKT, which in turn activate pathways to promote cell survival, invasion and migration. The upregulation, altered subcellular localization and associated signaling functions of PTK6/BRK in tumor cells make it a promising target for cancer therapy (6).