A5071886776- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Cancer-related Molecular Pathways
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Bacterial Genetics and Biotechnology
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Cancer Research and Treatments
- Microbial Community Ecology and Physiology
- Protist diversity and phylogeny
- RNA modifications and cancer
- Metabolism, Diabetes, and Cancer
- Cardiomyopathy and Myosin Studies
- Neuroscience and Neural Engineering
- Cellular transport and secretion
- Advanced Breast Cancer Therapies
- 14-3-3 protein interactions
- Growth Hormone and Insulin-like Growth Factors
- Monoclonal and Polyclonal Antibodies Research
- Microbial Natural Products and Biosynthesis
- Cutaneous lymphoproliferative disorders research
- PARP inhibition in cancer therapy
University of California, Davis
2015-2025
University of Iowa
2006-2023
University of Wisconsin–Madison
1997-2016
University of Calgary
2006
Bristol-Myers Squibb (United States)
1996-1997
University of California, San Francisco
1996
Max Planck Society
1990-1991
Max Planck Institute of Biochemistry
1988-1991
The existence of a large number receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) raises the question how particular receptor selectively regulates specific targets. We provide insight into this by identifying prototypical macromolecular signaling complex. beta(2) adrenergic was found be directly associated with one its ultimate effectors, class C L-type calcium channel Ca(v)1.2. This complex also contained G protein, an adenylyl cyclase, cyclic adenosine...
Rapid glutamatergic synaptic transmission is mediated by ionotropic glutamate receptors and depends on their precise localization at postsynaptic membranes opposing the presynaptic neurotransmitter release sites. Postsynaptic ofN-methyl-d-aspartate-type may be synapse-associated proteins (SAPs) SAP90, SAP102, chapsyn-110. SAPs contain three PDZ domains that can interact with C termini of such asN-methyl-d-aspartate receptor subunits carry a serine or threonine -2 position valine, isoleucine,...
The molecular basis of long-term potentiation (LTP), a long-lasting change in synaptic transmission, is fundamental interest because its implication learning. Usually LTP depends on Ca 2+ influx through postsynaptic N -methyl- d -aspartate (NMDA)-type glutamate receptors and subsequent activation /calmodulin-dependent protein kinase II (CaMKII). For understanding it crucial to know how CaMKII localized targets kinases often are targeted their substrates by adapter proteins. Here we show that...
Cyclin G2, together with cyclin G1 and I, defines a novel family expressed in terminally differentiated tissues including brain muscle. G2 expression is up-regulated as cells undergo cell cycle arrest or apoptosis response to inhibitory stimuli independent of p53 (Horne, M., Donaldson, K., Goolsby, G., Tran, D., Mulheisen, Hell, J. Wahl, A. (1997) <i>J. Biol. Chem.</i> 272, 12650–12661). We tested the hypothesis that may be negative regulator progression found ectopic induces formation...
Despite the recent identification of transcriptional regulatory circuitry involving SOX2, NANOG, and OCT-4, intracellular signaling networks that control pluripotency human embryonic stem cells (hESCs) remain largely undefined. Here, we demonstrate an essential role for serine/threonine protein kinase mammalian target rapamycin (mTOR) in regulating hESC long-term undifferentiated growth. Inhibition mTOR impairs pluripotency, prevents cell proliferation, enhances mesoderm endoderm activities...
Phosphorylation by cAMP-dependent protein kinase (PKA) regulates a vast number of cellular functions. An important target for PKA in brain and heart is the class C L-type Ca(2+) channel (Ca(v)1.2). phosphorylates serine 1928 central, pore-forming alpha(1C) subunit this channel. Regulation activity requires proper balance between phosphorylation dephosphorylation. For fast specific signaling, recruited to an A anchor (Davare, M. A., Dong, F., Rubin, C. S., Hell, J. W. (1999) Biol. Chem. 274,...
We describe the isolation and characterization of cDNAs encoding full-length human murine cyclin G1 a novel homologue this designated G2. Cyclin is expressed at high levels in skeletal muscle, ovary, kidney. Following an initial up-regulation from early to G1/S phase, mRNA constitutively throughout cell cycle T B lines. In contrast, stimulated peripheral cells, maximal phase declines progression. parallel p53 expression lymphocytes; however, several Burkitt's lymphomas, lymphocytes treated...
The cAMP-dependent protein kinase (PKA) controls a large number of cellular functions. One critical PKA substrate in the brain and heart is L-type Ca2+ channel Cav1.2, activity which upregulated by PKA. main phosphorylation site serine 1928 central pore forming α11.2 subunit Cav1.2. bound to Cav1.2 within macromolecular signaling complex consisting β2 adrenergic receptor, trimeric Gs protein, adenylyl cyclase for fast, localized, hence specific [Davare, M. A., Avdonin, V., Hall, D. D.,...
Human cyclin G2 together with its closest homolog G1 defines a novel family of cyclins (Horne, M. C., Goolsby, G. L., Donaldson, K. Tran, D., Neubauer, M., and Wahl, A. F. (1996)J. Biol. Chem. 271, 6050–6061). Cyclin is highly expressed in the immune system where immunologic tolerance subjects self-reactive lymphocytes to negative selection clonal deletion via apoptosis. Here we investigated effect growth inhibitory signals on mRNA abundance different maturation stage-specific murine B cell...
The L-type Ca 2+ channel (Ca V 1.2) is essential for cardiac excitation–contraction coupling. To contribute to the inward flux that drives -induced-Ca -release, 1.2 channels must be expressed on sarcolemma; thus regulatory mechanisms tune expression meet contractile demand are an emerging area of research. A ubiquitously protein called 14-3-3 has been proposed affect trafficking in nonmyocytes; however, whether similar effects cardiomyocytes unknown. preferentially binds...
We determined the minimal size of genomic region necessary for gas vesicle synthesis in halophilic archaebacteria by transformation experiments, comparative DNA sequence analysis and investigation (Vac) mutants. The comparison three regions encoding vesicles Halobacterium halobium (p-vac- c-vac-region) Haloferax mediterranei (mc-vac-region) indicates high similarity throughout a contiguous 9 kbp. In each case, this area encompassed at least 13 open reading frames (ORFs). Ten these ORFs (gvpD...
The L-type Ca(2+) channel Ca(v)1.2 forms macromolecular signaling complexes that comprise the β(2) adrenergic receptor, trimeric G(s) protein, adenylyl cyclase, and cAMP-dependent protein kinase (PKA) for efficient in heart brain. phosphatases PP2A PP2B are part of this complex. counteracts increase activity by PKA other kinases, whereas can either augment or decrease currents cardiomyocytes depending on precise experimental conditions. We found binds to two regions C-terminus central,...
Definition of cell cycle control proteins that modify tumor resistance to estrogen (E2) signaling antagonists could inform clinical choice for receptor positive (ER+) breast cancer (BC) therapy. Cyclin G2 (CycG2) is upregulated during arrest responses cellular stresses and growth inhibitory signals its gene, CCNG2, directly repressed by E2-bound ER complexes. Our previous studies showed blockade HER2, PI3K mTOR upregulates CycG2 expression in HER2+ BC cells, overexpression induces arrest....
L-type CaV1.2 channels are key regulators of gene expression, cell excitability and muscle contraction. organize in clusters throughout the plasma membrane. This channel organization has been suggested to contribute concerted activation adjacent (e.g. cooperative gating). Here, we tested hypothesis that dynamic intracellular perimembrane trafficking is critical for formation dissolution functional mediating gating. We found moves vesicular structures circular tubular shape with diverse...
Increased vascular Ca
Abstract The CCNG2 gene that encodes the unconventional cyclin G2 was one of few genes up-regulated on anti–human epidermal growth factor receptor 2 (HER2) antibody–mediated inhibition HER2 signaling. purpose this study to explore how signaling modulates expression and effect elevated breast cancer cell growth. Treatment cells overexpress (BT474, SKBr3, MDAMB453) with anti-HER2 antibody trastuzumab or its precursor 4D5 markedly mRNA in vitro vivo, as shown by real-time PCR. Immunoblot...