The tyrosine kinase Tec belongs to a new group of structurally related nonreceptor tyrosine kinases that also includes Btk and Itk. Previous studies have suggested that these kinases have lineage-specific roles, with Tec being involved mainly in the regulation of cytokine-mediated myeloid cell growth and differentiation. In this study, we investigated expression and activation of Tec in human B...

Mast cells play critical roles during immune responses to the bacterial endotoxin lipopolysaccharide (LPS) that can lead to fatal septic hypothermia [1], [2], [3]. IL-2 inducible T cell kinase (ITK) and Bruton's tyrosine kinase (BTK) are non-receptor tyrosine kinases that act downstream of numerous receptors, and have been shown to modulate mast cell responses downstream of FcεRIα [4], however,...

X-linked agammaglobulinemia (XLA) is a rare genetic disorder caused by mutations in the Bruton's tyrosine kinase (BTK) gene. These mutations cause defects in early B cell development. A patient with no circulating B cells and low serum immunoglobulin isotypes was studied as were his mother and sister. Monocyte BTK protein expression was evaluated by flow cytometry. The mutation was determined u...

We studied the immune response to Bacillus thuringiensis kurstaki (Btk) in susceptible (Bt-RS) and resistant (Bt-R) Trichoplusia ni after exposure to low doses of Btk and injection with Escherichia coli. We measured the levels of resistance, the expression profiles of hemolymph proteins, the phenoloxidase (PO) activity, and the differential number of circulating hemocytes in resistant and susce...

The B-cell receptor (BCR) signaling pathway has gained significant attention as a therapeutic target in B-cell malignancies. Recently, several drugs that target the BCR signaling pathway, especially the Btk inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicates that pharmacological inhibition of BCR pathway holds promise in B-cell lym...

In a systematic effort to design potent inhibitors of the anti-apoptotic tyrosine kinase BTK (Bruton's tyrosine kinase) as anti-leukemic agents with apoptosis-promoting and chemosensitizing properties, we have constructed a three-dimensional homology model of the BTK kinase domain. Our modeling studies revealed a distinct rectangular binding pocket near the hinge region of the BTK kinase domain...

Acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells characterized by diverse cytogenetic and molecular abnormalities. Although chemotherapy can cure a major proportion of ALL patients, some may relapse and develop serious complications including death. Bruton tyrosine kinase (Btk), a cytoplasmic protein mainly expressed in hematopoietic cells, and nuclear fac...

Bruton's tyrosine kinase (Btk) is a cytoplasmic signaling molecule that is crucial for precursor (pre-B) cell differentiation in humans. In this study, we show that during the transition of large cycling to small resting pre-B cells in the mouse, Btk-deficient cells failed to efficiently modulate the expression of CD43, surrogate L chain, CD2, and CD25. In an analysis of the kinetics of pre-B c...

In understanding the mechanisms of cholesterol in the pathogenesis of atherosclerosis, previous studies from other laboratories have demonstrated that cholesterol crystals (CC) induce scavenger receptor CD36 expression and NLRP3-mediated inflammasome formation. In elucidating the mechanisms by which CC could enhance CD36 expression and foam cell formation, here we report that CC via NADPH and x...

We analyzed the cause of agammaglobulinemia in a girl whose father had been diagnosed as having X-linked agammaglobulinemia (XLA). Flow cytometric analysis revealed the lack of peripheral B cells with the block of B-cell differentiation in the stages between pro-B cells and pre-B cells in the bone marrow, and the defect of the Bruton tyrosine kinase (BTK) expression on monocytes. We found a BTK...