A5037758372- Protein Kinase Regulation and GTPase Signaling
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Caveolin-1 and cellular processes
- Erythrocyte Function and Pathophysiology
- PI3K/AKT/mTOR signaling in cancer
- Metabolism, Diabetes, and Cancer
- Cell death mechanisms and regulation
- Protein Structure and Dynamics
- Melanoma and MAPK Pathways
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Ion channel regulation and function
- Phagocytosis and Immune Regulation
- Enzyme Structure and Function
- Peptidase Inhibition and Analysis
- Galectins and Cancer Biology
- Signaling Pathways in Disease
- Cancer-related Molecular Pathways
- Sphingolipid Metabolism and Signaling
- Glycosylation and Glycoproteins Research
- Ion Transport and Channel Regulation
- Hippo pathway signaling and YAP/TAZ
- Calcium signaling and nucleotide metabolism
The University of Texas Health Science Center at Houston
2015-2024
The University of Texas MD Anderson Cancer Center
2013-2024
The University of Texas at Austin
2010-2023
Cancer Research UK
2022
Laboratoire d’immunologie intégrative du cancer
2022
University of Cambridge
2022
Virginia Commonwealth University
2021
National Institute of Environmental Health Sciences
2021
Translational Genomics Research Institute
2021
University of Houston
2020
The small guanine nucleotide binding protein Ras participates in a growth promoting signal transduction pathway. mechanism by which interaction of with the kinase Raf leads to activation was studied. targeted plasma membrane addition COOH-terminal localization signals K-ras. This modified form (RafCAAX) activated same extent as coexpressed oncogenic mutant Ras. Plasma rather than farnesylation or presence additional sequence accounted for RafCAAX. RafCAAX completely independent Ras; it...
Localization of signaling complexes to specific microdomains coordinates signal transduction at the plasma membrane. Using immunogold electron microscopy membrane sheets coupled with spatial point pattern analysis, we have visualized morphologically featureless microdomains, including lipid rafts, in situ and high resolution. We find that an inner-plasma raft marker displays cholesterol-dependent clustering a mean diameter 44 nm occupy 35% cell surface. Cross-linking outer-leaflet protein...
Ha-, N-, and Ki-Ras are ubiquitously expressed in mammalian cells can all interact with the same set of effector proteins. We show here, however, that vivo there marked quantitative differences ability Ki- Ha-Ras to activate Raf-1 phosphoinositide 3-kinase. Thus, both recruits plasma membrane more efficiently than is a potent activator membrane-recruited Ha-Ras. In contrast, 3-kinase Ki-Ras. Interestingly, recruit significantly increased when hypervariable region shortened so spacing GTPase...
Plasma membrane compartmentalization imposes lateral segregation on proteins that is important for regulating signal transduction. We use computational modeling of immunogold spatial point patterns intact plasma sheets to test different models inner organization. find at the nanoscale level but show a classical raft model preexisting stable domains into which lipid partition incompatible with generated by labeling palmitoylated marker protein. Rather, approximately 30% protein exists in...
Using quantitative light microscopy and a modified immunoelectron microscopic technique, we have characterized the entry pathway of cholera toxin binding subunit (CTB) in primary embryonic fibroblasts. CTB trafficking to Golgi complex was identical caveolin-1null (Cav1−/−) mouse fibroblasts (MEFs) wild-type (WT) MEFs. Cav1−/− MEFs predominantly clathrin dynamin independent but relatively cholesterol dependent. Immunoelectron used quantify budded surface-connected caveolae identify...
Ras proteins must be localized to the inner surface of plasma membrane biologically active. The motifs that effect targeting consist a C-terminal CAAX motif plus second signal comprising palmitoylation adjacent cysteine residues or presence polybasic domain. In this study, we examined how access cell after processing is completed in endoplasmic reticulum (ER). We show palmitoylated proteins, addition being at membrane, are found throughout exocytic pathway and accumulate Golgi region when...
Plasma membrane depolarization can trigger cell proliferation, but how potential influences mitogenic signaling is uncertain. Here, we show that plasma induces nanoscale reorganization of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate not other anionic phospholipids. K-Ras, which targeted to the by electrostatic interactions with phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization-induced changes K-Ras organization occur fibroblasts, excitable...
Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times volume internalized by clathrin-mediated pathway, forming major pathway involved in uptake fluid bulk membrane fibroblasts. Electron tomographic analysis 3D morphology earliest shows they are multidomain organelles...
Polymerase I and transcript release factor (PTRF)/Cavin is a cytoplasmic protein whose expression obligatory for caveola formation. Using biochemistry fluorescence resonance energy transfer–based approaches, we now show that family of related proteins, PTRF/Cavin-1, serum deprivation response (SDR)/Cavin-2, SDR-related gene product binds to C kinase (SRBC)/Cavin-3, muscle-restricted coiled-coil (MURC)/Cavin-4, forms multiprotein complex associates with caveolae. This can constitutively...