Reconstitution of Btk Signaling by the Atypical Tec Family Tyrosine Kinases Bmx and Txk

Abstract

Bruton's tyrosine kinase (Btk) 1 is a member of the Tec family of nonreceptor protein-tyrosine kinases (PTKs) that includes Bmx, Itk, Tec, and Txk (reviewed in Ref. 1). Tec family PTKs are characterized by an NH 2 -terminal pleckstrin homology (PH) domain followed by a Tec homology domain (containing a Zn 2ϩ -binding Btk motif and a proline-rich region), a Src-homology 3 (SH3) and SH2 domain, and a COOH-terminal kinase domain (1, 2) (Fig. 1). Tec PTKs share 50 -60% amino acid sequence identity and are predominately expressed by cells of the immune system (1). Bmx and Txk are somewhat atypical family members: Bmx shares little sequence homology with other Tecs within the proline-rich and SH3 domains; Txk is particularly atypical at the NH 2 terminus, lacking the PH and Tec homology domains (Fig.

G13α-mediated PYK2 Activation

“…To examine the potential for Tec kinases to activate the SRF in HeLa cells, we have tested whether Bruton's tyrosine kinase (BTK) enhances transcription of the SRE-luciferase reporter. Arguing that expression of BTK should be functionally equivalent to the expression of other Tec kinases, Bmx, Txk, Tec, and Itk all reconstitute BTK signaling in cell lines deficient for BTK (24). We find that a constitutively active form of BTK induces only a 2-3-fold increase in reporter gene activity, while wild type PYK2 induces a 20-fold enhancement; however, the combination of PYK2 and BTK leads to a 60-fold increase.…”

A Novel Role for Bruton's Tyrosine Kinase in Hepatocyte Growth Factor-mediated Immunoregulation of Dendritic Cells

“…Initially, whether HGF treatment induces Btk activation in DCs was examined. Immature BMDCs (CD11c ϩ CD8␣ Ϫ ) prepared from BALB/c mice were treated with HGF for varying times and Btk activation was determined by measuring Tyr phosphorylation of Btk as described (33). Treatment of BMDCs with HGF induced a transient increase in Tyr phosphorylation of Btk, which peaked within 5 min and returned to basal levels by 10 min after HGF treatment (Fig.…”

Kinase Activation of the Non-receptor Tyrosine Kinase Etk/BMX Alone Is Sufficient to Transactivate STAT-mediated Gene Expression in Salivary and Lung Epithelial Cells

“…The precise biological function of Etk in epithelial cells is not well established. The Etk/BMX-mediated cellular responses have mainly been studied by using a dominant negative form of Etk to attenuate its function (1,15) or a cytokine stimulation/ antigen cross-linking approach to activate Etk/BMX kinase activities (1,4). These studies have yielded important information, however, generally addressed only a particular experimental condition without determining the specificity of each individual signaling cascade.…”

“…3). For example, Etk/BMX compensates for the lack of Btk activity in B-cell receptor signal transduction by reconstituting phospholipase C␥2-dependent responses in Btk-deficient DT40 cells (4). However, these activities may not be the primary in vivo function of Etk/BMX, since Etk/BMX is predominantly expressed in lung and prostate tissues, as well as in salivary epithelial, endothelial, and granulomonocytic cells (1, 2, and this report), but not in B-cells.…”