a new article published in the journal Aging, Borras et al. report that Ras-GRF1 homozigous deletion increases both median and maximum longevity in laboratory mice [1]. The human Ras, superfamily now counts more than 150 different proteins subdivided into five different protein families: Ras, Rho, Rab, Arf and Ran. These protein families regulate many cellular processes [2] including cellular d...

Author correspondence to: Surangani Dharmawardhane PhD, Department of Biochemistry, School of Medicine, Medical Sciences Campus University of Puerto Rico, PO Box 365067, San Juan, PR00936. Tel: 787-758-2525 ext. 1630/1610 • Fax: 787-274-8724 • E-mail: [email protected] & Cornelis P. Vlaar PhD, Department of Pharmaceutical Sciences, School of Pharmacy, Medical Sciences Campus University of Puerto Ric...

Cellular and molecular pathways link thrombosis and innate immune system during sepsis. Extrinsic pathway activation of protease thrombin through FVIIa and tissue factor (TF) in sepsis help activate its endothelial cell (EC) membrane Protease Activated Receptor 1 (PAR-1). Thrombin adjusts the EC cycle through activation of G proteins (G12/13), and later through Rho GEFs (guanine nucleotide exch...

BACKGROUND Transport of molecules from one subcellular compartment to another involves the recruitment of cytosolic coat protein complexes to a donor membrane to concentrate cargo, deform the membrane and ultimately to form an independent carrier. Small-GTP-binding proteins of the Arf family are central to many membrane trafficking events. Arfs are activated by guanine nucleotide exchange facto...

Ca2+ sensitivity of smooth muscle and nonmuscle myosin II reflects the ratio of activities of myosin light-chain kinase (MLCK) to myosin light-chain phosphatase (MLCP) and is a major, regulated determinant of numerous cellular processes. We conclude that the majority of phenotypes attributed to the monomeric G protein RhoA and mediated by its effector, Rho-kinase (ROK), reflect Ca2+ sensitizati...

Ras proteins can activate at least three classes of downstream target proteins: Raf kinases, phosphatidylinositol-3 phosphate (PI3) kinase, and Ral-specific guanine nucleotide exchange factors (Ral-GEFs). In NIH 3T3 cells, activated Ral-GEFs contribute to Ras-induced cell proliferation and oncogenic transformation by complementing the activities of Raf and PI3 kinases. In PC12 cells, activated ...

Generalized epilepsy with febrile seizures plus (GEFS+) is a benign epileptic syndrome of humans. It is characterized by febrile and afebrile generalized seizures that occur predominantly in childhood and respond well to standard antiepileptic therapy. A mutation in the b1-subunit of the voltage-gated sodium channel, linked to chromosome 19q13 (GEFS+ type 1) has been found in one family. For fo...

G protein-coupled receptor (GPCR) activation elicits neutrophil responses such as chemotaxis and reactive oxygen species (ROS) formation, which depend on the small G protein Rac and are essential for host defense. P-Rex and Vav are two families of guanine-nucleotide exchange factors (GEFs) for Rac, which are activated through distinct mechanisms but can both control GPCR-dependent neutrophil re...