Mps1 Mediated Phosphorylation of Hsp90 Confers Renal Cell Carcinoma Sensitivity and Selectivity to Hsp90 Inhibitors.

The molecular chaperone Hsp90 protects deregulated signaling proteins that are vital for tumor growth and survival. Tumors generally display sensitivity and selectivity toward Hsp90 inhibitors; however, the molecular mechanism underlying this phenotype remains undefined. We report that the mitotic checkpoint kinase Mps1 phosphorylates a conserved threonine residue in the amino-domain of Hsp90.

CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain.

CD2AP, an adapter protein containing multiple SH3 domains, plays a critical role in kidney function. Mice lacking CD2AP die soon after birth because of kidney failure. In the kidney, CD2AP is expressed in glomerular podocytes, which suggests that it may play a role in a specialized adhesion complex known as the slit diaphragm.

Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis.

Background: Several lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis.

Methods: The roles of alphabeta and gammadelta T cells in the pathogenesis of glomerulonephritis were investigated in a model of nephrotoxic nephritis in mice deficient in either T-cell population [T-cell receptor (TCR)beta and TCRdelta knockout mice]. The model, induced by the injection of rabbit anti-mouse glomerular basement membrane antibody, is characterized by the development of proteinuria and glomerular damage over a 21-day observation period in wild-type mice.

Glomerular inflammation: use of genetically deficient mice to elucidate the roles of leukocyte adhesion molecules and Fc-gamma receptors in vivo.

Single gene knock-outs in mice have been used to define the biological role of leukocyte adhesion receptors, Fc-gamma receptors and complement in animal models of immune complex glomerulonephritis. These studies have shown important differences in the role of P-selectin in glomerular inflammation and inflammation at other sites, and have given a new appreciation of the dominant role played by Fc-gamma receptors in immune complex-induced glomerular injury.

P-selectin deficiency exacerbates experimental glomerulonephritis: a protective role for endothelial P-selectin in inflammation.

P-selectin is a leukocyte adhesion receptor present in endothelial cells and platelets. We examined the role of P-selectin in the autologous phase of an accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis using P-selectin-deficient mice and chimeric mice expressing P-selectin only in platelets or endothelial cells. P-selectin-deficient mice exhibited more severe glomerular damage with increased interstitial mononuclear leukocytic infiltrates, and had significantly increased proteinuria and mortality when compared to wild-type mice.