BTK
BTK (Bruton tyrosine kinase, also known as ATK, XLA, PSCTK1, AGMX1 and IMD1) is a non-receptor tyrosine kinase of the TEC subfamily. It is indispensable for B lymphocyte development, differentiation and signalling. Browse Assay Genie's current range of BTK research reagents below, or read on for the biology behind the target.
BTK is a non-receptor tyrosine kinase that sits at the centre of B-cell antigen receptor (BCR) signalling. When antigen binds the BCR, BTK is engaged at the plasma membrane and phosphorylates PLCG2 at several sites, working closely with the adapter protein BLNK. This starts the downstream pathway of calcium mobilisation followed by activation of protein kinase C (PKC) family members, ultimately leading to B-cell activation. BTK acts as a platform that brings together a diverse array of signalling proteins and is also implicated in cytokine receptor signalling.
Beyond the BCR, BTK contributes to innate and adaptive immunity as a component of the Toll-like receptor (TLR) pathway, and is a critical regulator of TLR9 activation in splenic B-cells. It induces tyrosine phosphorylation of TIRAP, leading to TIRAP degradation, and links TLR8 and TLR9 to NF-kappa-B, whose activity it induces. BTK also mediates phosphorylation of NLRP3 to promote NLRP3 inflammasome assembly, and phosphorylates DDX41 in STING1-mediated induction of the type I interferon response. It has a dual role in the regulation of apoptosis.
BTK also influences transcription. It transiently phosphorylates GTF2I in response to BCR engagement, after which GTF2I moves to the nucleus to bind regulatory enhancer elements. ARID3A and NFAT are further transcriptional targets, and BTK is required for the formation of functional ARID3A DNA-binding complexes, although there is no evidence that BTK binds DNA directly. The BTK gene belongs to the protein kinase superfamily and the Tyr protein kinase family, and its product contains pleckstrin homology, SH2 and SH3 domains. Mutations in the BTK gene cause X-linked agammaglobulinaemia type 1, an immunodeficiency marked by failure to produce mature B lymphocytes and failure of Ig heavy chain rearrangement. Alternative splicing yields multiple isoforms. The mouse ortholog is Btk.
BTK is indispensable for B lymphocyte development, differentiation and BCR signalling, making it a core target for studying B-cell activation.
BTK is a component of the TLR pathway, regulates TLR9 activation in splenic B-cells and links TLR8 and TLR9 to NF-kappa-B.
BTK phosphorylates NLRP3 to promote inflammasome assembly and phosphorylates DDX41 in STING1-mediated type I interferon induction.
Mutations in the BTK gene cause X-linked agammaglobulinaemia type 1, characterised by failure to produce mature B lymphocytes.
BTK is a non-receptor tyrosine kinase essential for B-cell development, differentiation and signalling. After BCR engagement it phosphorylates PLCG2, driving calcium mobilisation and PKC activation. It also acts in TLR signalling, induces NF-kappa-B activity and promotes NLRP3 inflammasome assembly.
BTK was previously named Bruton agammaglobulinemia tyrosine kinase, and its aliases include ATK, XLA, PSCTK1, AGMX1 and IMD1. UniProt lists the protein as Tyrosine-protein kinase BTK. Alternative splicing of the BTK gene results in multiple transcript variants encoding different isoforms.
Mutations in BTK cause X-linked agammaglobulinaemia type 1, an immunodeficiency with failure to produce mature B lymphocytes. A mouse ortholog, Btk, exists; check the datasheet of any product for its validated reactivity.
Other B-cell receptor, Toll-like receptor, inflammasome and interferon pathway proteins connected to BTK signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q06187; product specifications from Assay Genie datasheets.