Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.

Btk (Bruton tyrosine kinase also known as BPK or ATK) is a member of the TEC family of non-receptor protein tyrosine kinase which includes Bmx, Itk and TEC. Btk is composed of a pleckstrin domain, an SH3 and SH2 domain, a catalytic kinase domain and a TEC homology domain (1). Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the SH3 domain via a transphosphorylation mechanism, which for Bruton's tyrosine kinase (Btk) affects tyrosine 223. (2). Similar to Etk-TNFR2 interaction, Btk interacts with Fas, a member of the TNFR family involved in apoptosis in a ligand-independent manner (3). Btk can be activated through intramolecular autophosphorylation at tyrosine 551 and that Btk autophosphorylation is required for Btk catalytic functions (4).

A phospho specific peptide corresponding to residues surrounding tyrosine 223 of human BTK was used as an immunogen. This antibody detects BTK phosphorylated on tyrosine 223.

Rabbit

50 mM Tris-Glycine (pH 7.4), 0.15 M NaCl, 40% Glycerol, 0.01% sodium azide and 0.05% BSA.

1. Tsukada, S., et al (1993) Cell 72, 279-290<br>2. Rawlings, DJ et al. Immunol. 7, 237-246<br>3. Vassilev, AZ et al.. 1999. J. Biol. Chem. 274:1646-1656<br>4. Mahajan S, et al. Mol Cell Biol. 1995;15:5304<br>

Human

Tyrosine-protein kinase BTK, Agammaglobulinemia tyrosine kinase, ATK, B-cell progenitor kinase, BPK, Bruton tyrosine kinase, BTK, AGMX1, ATK, BPK

WB~~1:100000~500000

Function Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK plays also a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis. Cellular_Location Cytoplasm. Cell membrane; Peripheral membrane protein. Nucleus. Note=In steady state, BTK is predominantly cytosolic. Following B-cell receptor (BCR) engagement by antigen, translocates to the plasma membrane through its PH domain. Plasma membrane localization is a critical step in the activation of BTK. A fraction of BTK also shuttles between the nucleus and the cytoplasm, and nuclear export is mediated by the nuclear export receptor CRM1 Tissue_Location Predominantly expressed in B-lymphocytes.