Communication between different signaling pathways enables cells to coordinate the responses to diverse environmental signals. Activation of the transmembrane growth factor precursors plays a critical role in this communication and often involves metalloprotease-mediated proteolysis. Stimulation of G protein-coupled receptors (GPCR) transactivates the EGF receptors (EGFRs), which occurs via a m...

Ligands that activate the epidermal growth factor receptor (EGFR) are synthesized as membrane-anchored precursors that appear to be proteolytically released by members of the ADAM family of metalloproteases. Because membrane-anchored EGFR ligands are thought to be biologically active, the role of ligand release in the regulation of EGFR signaling is unclear. To investigate this question, we use...

BACKGROUND Activators of PPARs, particularly PPARγ, may be effective neuroprotective drugs against inflammatory responses in cerebral ischemia and reperfusion injury. Ursolic acid (UA) may act as a PPARγ agonist and serve as an anti-inflammatory agent. In this study, we used a rat middle cerebral artery occlusion and reperfusion model to examine how UA acts as a neuroprotective agent to modulat...

C ELL--cell and cell-matrix adhesion, as well as proteolysis of the extracellular matrix, are vital for normal processes such as tissue morphogenesis and wound healing, as well as for pathologies such as tumor cell invasion and metastasis. A variety of cell surface adhesion proteins and proteases are important players in these events. Families of membrane-anchored cell surface adhesion molecule...

GPR37 is an orphan G protein-coupled receptor (GPCR) implicated in several neurological diseases and important physiological pathways the brain. We previously reported that its long N-terminal ectodomain undergoes constitutive metalloprotease-mediated cleavage shedding, which have been rarely described for class A GPCRs. Here, we demonstrate protease cleaves at Glu167?Gln168 a disintegrin metal...

Molecular modeling is a set of computational techniques for construction of 3D structure of a protein especially membrane bound proteins whose structures can not be elucidated using experimental techniques. These techniques has been applied in the study of membrane metalloproteases for comparing wild and mutated enzymes, docking inhibitors in the catalytic site and examination of binding pocket...