21 research outputs found
Don't stop your heart in front of your family: family as a bystander is associated with poor outcome of bystander-witnessed, bystander-CPR-performed out-of-hospital cardiac arrest
CPR initiated after telephone-assisted instruction produces a better outcome of bystander-witnessed out-of-hospital cardiac arrests than no bystander CPR but is less effective than CPR on the bystander's own initiative
Experimental investigation of the passive control of unsteady cloud cavitation using miniature vortex generators (MVGs)
High plasma D-dimer level is associated with decreased survival in patients with lung cancer: a meta-analysis
Designing Lean Processes With Improved Service Quality: An Application in Financial Services
Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population
Membrane Targeting of Grb2-associated Binder-1 (Gab1) Scaffolding Protein through Src Myristoylation Sequence Substitutes for Gab1 Pleckstrin Homology Domain and Switches an Epidermal Growth Factor Response to an Invasive Morphogenic Program
The hepatocyte growth factor receptor tyrosine kinase Met promotes cell dissociation and the inherent morphogenic program of epithelial cells. In a search for substrates downstream from Met, we have previously identified the Grb2-associated binder-1 (Gab1) as critical for the morphogenic program. Gab1 is a scaffold protein that acts to diversify the signal downstream from the Met receptor through its ability to couple with multiple signal transduction pathways. Gab1 contains a pleckstrin homology (PH) domain with specificity for phosphatidylinositol 3,4,5-trisphosphate. The phospholipid binding capacity of the Gab1 PH domain is required for the localization of Gab1 at sites of cell-cell contact in colonies of epithelial cells and for epithelial morphogenesis, suggesting that PH domain-dependent subcellular localization of Gab1 is a prerequisite for function. We have investigated the requirement for membrane localization of Gab1 for biological activity. We show that substitution of the Gab1 PH domain with the myristoylation signal from the c-Src protein is sufficient to replace the Gab1 PH domain for epithelial morphogenesis. The membrane targeting of Gab1 enhances Rac activity in the absence of stimulation and switches a nonmorphogenic noninvasive response to epidermal growth factor to a morphogenic invasive program. These results suggest that the subcellular localization of Gab1 is a critical determinant for epithelial morphogenesis and invasiveness