Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses.

Misfolded proteins are caused by genomic mutations, aberrant splicing events, translation errors or environmental factors. The accumulation of misfolded proteins is a phenomenon connected to several human disorders, and is managed by stress responses specific to the cellular compartments being affected. In wild-type cells these mechanisms of stress response can be experimentally induced by expressing recombinant misfolded proteins or by incubating cells with large concentrations of amino acid analogues.

Glycoprotein VI oligomerization in cell lines and platelets.

Background: Glycoprotein VI (GPVI) is a physiologic receptor for collagen expressed at the surface of platelets and megakaryocytes. Constitutive dimerization of GPVI has been proposed as being necessary for the interaction with collagen, although direct evidence of dimerization has not been reported in cell lines or platelets.

Objectives: To investigate oligomerization of GPVI in transfected cell lines and in platelets under non-stimulated conditions.

Delineation of the region in the glycoprotein VI tail required for association with the Fc receptor gamma-chain.

The glycoprotein VI (GPVI).Fc receptor gamma-chain (FcRgamma-chain) complex is the major activation receptor for collagen on platelets. GPVI cross-linking mediates activation through tyrosine phosphorylation of an ITAM (immunoreceptor tyrosine-based activation motif) in the FcR gamma-chain by Src family kinases.

Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling.

The glycoprotein VI (GPVI)-Fc receptor (FcR) gamma-chain complex, a key activatory receptor for collagen on platelet surface membranes, is constitutively associated with the Src family kinases Fyn and Lyn. Molecular cloning of GPVI has revealed the presence of a proline-rich domain in the sequence of GPVI cytoplasmic tail which has the consensus for interaction with the Src homology 3 (SH3) domains of Fyn and Lyn. A series of in vitro experiments demonstrated the ability of the SH3 domains of both Src kinases to bind the proline-rich domain of GPVI.