A5082828872- Pancreatitis Pathology and Treatment
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic and Hepatic Oncology Research
- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- Receptor Mechanisms and Signaling
- Liver Disease Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Ion channel regulation and function
- Diet, Metabolism, and Disease
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Diabetes and associated disorders
- Neuroscience and Neuropharmacology Research
- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- Nitric Oxide and Endothelin Effects
- Mitochondrial Function and Pathology
- PI3K/AKT/mTOR signaling in cancer
- HER2/EGFR in Cancer Research
- Blood disorders and treatments
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Cellular transport and secretion
Cedars-Sinai Medical Center
2016-2025
University of California, Los Angeles
2012-2024
Johns Hopkins University
2022
Los Angeles Medical Center
2022
Stanford University
2022
Walter Reed National Military Medical Center
2022
VA Greater Los Angeles Healthcare System
2011-2019
West Los Angeles College
2014
Center for Excellence in Education
2013
VA West Los Angeles Medical Center
2013
A close correlation was observed between intracellular Ca2+ pool depletion and refilling the onset of DNA synthesis proliferation DDT1MF-2 smooth muscle cells. The pump inhibitors 2,5-di-tert-butyl-hydroquinone (DBHQ) thapsigargin (TG) specifically emptied identical inositol 1,4,5-trisphosphate (InsP3)-sensitive pools both arrested cell growth at concentrations corresponding to blockade. However, an important distinction two with respect their reversibility action. Upon removal DBHQ from...
Persistent activation of protein kinase D (PKD) via C (PKC)-mediated signal transduction is accompanied by phosphorylation at Ser(744) and Ser(748) located in the catalytic domain loop, but whether PKC isoforms directly phosphorylate these residues, induce PKD autophosphorylation, or recruit intermediate upstream kinase(s) unclear. Here, we explore mechanism whereby activates response to cellular stimuli. We first assessed vitro PKC-PKD transphosphorylation activation. A PKD738-753 loop...
Epidemiologic data has linked obesity to a higher risk of pancreatic cancer, but the underlying mechanisms are poorly understood. To allow for detailed mechanistic studies in relevant model mimicking diet-induced and high-fat, high-calorie diet (HFCD) was given P48+/Cre;LSL-KRASG12D (KC) mice carrying pancreas-specific oncogenic Kras mutation. The were randomly allocated HFCD or control (CD). Cohorts sacrificed at 3, 6, 9 months tissues harvested further analysis. Compared CD-fed mice,...
This work confirms previous reports that CM4620, a small molecule inhibitor of Ca
Protein kinase D (PKD) is activated by phosphorylation in intact cells stimulated phorbol esters, cell permeant diacylglycerols, bryostatin, neuropeptides, and growth factors, but the critical activating residues PKD have not been identified. Here, we show that substitution of Ser<sup>744</sup> Ser<sup>748</sup> with alanine (PKD-S744A/S748A) completely blocked activation induced phorbol-12,13-dibutyrate (PDB) treatment as assessed autophosphorylation exogenous syntide-2 peptide substrate...
Protein kinase D (PKD) is a serine/threonine protein that activated by phorbol esters via C in intact cells. To assess the physiological significance of this putative pathway, we examined regulation PKD living cells mitogenic regulatory peptides and platelet-derived growth factors (PDGF). Our results demonstrate bombesin rapidly induces activation Swiss 3T3 cells, as shown autophosphorylation syntide-2 phosphorylation assays. Maximum (14-fold above base-line levels) was obtained 90 s after...
The importance of activation loop phosphorylation in the regulation protein kinase D (PKD/protein C (PKC) µ) activity has become controversial. In order to clarify mechanism(s) PKD activation, we developed a novel phosphospecific antibody recognizing phosphorylated Ser<sup>748</sup> (pS748). Western blot analysis with pS748 antibody, carried out variety forms and cell types including full-length transfected COS-7 HEK 293 cells, green fluorescent protein-PKD fusion either Swiss 3T3...
Activation of RAS proteins can lead to multiple outcomes by virtue regulated signal traffic through alternate effector pathways. We demonstrate that the protein RIN1 binds activated with an affinity (K d , 22 nM) similar observed for RAF1. At concentrations close their equilibrium dissociation constant values, and RAF1 compete directly binding. was also inhibit cellular transformation mutant RAS. This distinguishes from other effectors, which are enhancing. Blockade mediated binding domain...
Protein kinase D (PKD) is a protein serine that directly stimulated in vitro by phorbol esters and diacylglycerol the presence of phospholipids, activated esters, neuropeptides, platelet-derived growth factor via C (PKC) intact cells. Recently, oxidative stress was shown to activate transfected PKC isoforms tyrosine phosphorylation, but PKD activation not demonstrated. Here, we report initiated addition H2O2 (0.15–10 mm) quiescent Swiss 3T3 fibroblasts activates dose- time- dependent manner,...
The results presented here demonstrate that protein kinase D (PKD) and PKCη transiently coexpressed in COS-7 cells form complexes can be immunoprecipitated from cell lysates using specific antisera to PKD or PKCη. presence of immune was initially detected by vitro assays which reveal the an 80-kDa phosphorylated band addition 110-kDa corresponding autophosphorylated PKD. association between further verified Western blot analysis peptide phosphorylation exploited distinct substrate...
Intracellular Ca2+ pump expression and pool function are shown to be closely associated with growth proliferation of DDT1MF-2 hamster smooth muscle cells. The blocker thapsigargin induces sustained emptying entry cells into a quiescent G0-like state (Short, A. D., Bian, J., Ghosh, T. K., Waldron, R. T., Rybak, S. L., Gill, D. L. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 4986-4990). Using growth-arrested by exposure 3 microM for 24 h, treatment 20% serum 6 h without induced functional protein...
Protein kinase D (PKD) is a serine/threonine protein rapidly activated by G protein-coupled receptor (GPCR) agonists via C (PKC)-dependent pathway. Recently, PKD has been implicated in the regulation of long term cellular activities, but little known about mechanism(s) sustained activation. Here, we show that cell treatment with preferential PKC inhibitors GF 109203X or Gö 6983 blocked rapid (1–5-min) activation induced bombesin stimulation, this inhibition was greatly diminished at later...
Rapid protein kinase D (PKD) activation and phosphorylation via C (PKC) have been extensively documented in many cell types cells stimulated by multiple stimuli. In contrast, little is known about the role mechanism(s) of a recently identified sustained phase PKD response to G protein-coupled receptor agonists. To elucidate biphasic activation, we used Swiss 3T3 because expression these potently enhanced duration ERK DNA synthesis G(q)-coupled Cell treatment with preferential PKC inhibitors...
Epidemiological studies support strong links between obesity, diabetes, and pancreatic disorders including pancreatitis adenocarcinoma (PDAC). Type 2 diabetes (T2DM) is associated with insulin resistance, hyperglycemia, hyperinsulinemia, the latter due to increased secretion by beta-cells. We reported that high-fat diet-induced PDAC progression in mice activation of stellate cells (PaSC). investigated here effects high concentrations glucose on mouse human PaSC growth fibrosing responses....