Learn More
The Tec family of protein-tyrosine kinases (PTKs), that includes Tec, Itk, Btk, Bmx, and Txk, plays an essential role in phospholipase Cgamma (PLCgamma) activation following antigen receptor stimulation. This function requires activation of phosphatidylinositol 3-kinase (PI 3-kinase), which promotes Tec membrane localization through phosphatidylinositol(More)
The two lectin receptors, CLEC-2 and Dectin-1, have been shown to signal through a Syk-dependent pathway, despite the presence of only a single YXXL in their cytosolic tails. In this study, we show that stimulation of CLEC-2 in platelets and in two mutant cell lines is dependent on the YXXL motif and on proteins that participate in signaling by(More)
The recently discovered transmembrane 4 superfamily comprises a group of cell-surface proteins that are characterized by the presence of four hydrophobic domains, which are presumed to be membrane spanning. At least seven of these molecules are expressed on leukocytes, and it seems likely that they mediate signal transduction events that play a role in the(More)
Adapters can be defined as proteins that mediate intermolecular interactions within a signal transduction pathway and that lack both intrinsic enzymatic and transcriptional activity. Their essential role in lymphocyte signaling was revealed by recent analyses of mice and cell lines deficient in LAT, SLP-76 and BLNK. These and other adapters nucleate(More)
A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane metalloprotease that cleaves the extracellular regions from its transmembrane substrates. ADAM10 is essential for embryonic development and is implicated in cancer, Alzheimer, and inflammatory diseases. The tetraspanins are a superfamily of 33 four-transmembrane proteins(More)
The collagen receptor glycoprotein VI (GPVI) induces platelet activation through a similar pathway to that used by immune receptors. In the present study we have investigated the role of phosphatidylinositol 3-kinase (PI 3-kinase) in GPVI signalling. Our results show that collagen-related peptide {CRP: [GCP*(GPP*)(10)GCP*G](n); P*=hydroxyproline}, which is(More)
Loss of the tumor suppressor MMAC1 has been shown to be involved in breast, prostate and brain cancer. Consistent with its identification as a tumor suppressor, expression of MMAC1 has been demonstrated to reduce cell proliferation, tumorigenicity, and motility as well as affect cell-cell and cell-matrix interactions of malignant human glioma cells.(More)
The C-type lectin receptor CLEC-2 activates platelets through Src and Syk tyrosine kinases, leading to tyrosine phosphorylation of downstream adapter proteins and effector enzymes, including phospholipase-C gamma2. Signaling is initiated through phosphorylation of a single conserved tyrosine located in a YxxL sequence in the CLEC-2 cytosolic tail. The(More)
A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitous transmembrane metalloprotease that cleaves the extracellular regions from over 40 different transmembrane target proteins, including Notch and amyloid precursor protein. ADAM10 is essential for embryonic development and is also important in inflammation, cancer, and Alzheimer disease. However,(More)
TGF-beta plays an important role in immune regulation in vivo and affects T cell differentiation in vitro. Here we describe how TGF-beta modulates Th2 development in vitro and investigate its mechanisms of action. TGF-beta down-regulated Th2 development of naive CD4+ Mel-14high T cells derived from the DO11.10 ovalbumin-specific TCR-transgenic mouse, and(More)