Guanine triphosphate -binding proteins

BRASS LF, SHALLER CC, BELMONTE EJ (1987) Inositol 1,4,5-triphosphate-induced granule secretion in jdatelets. Evidence that the activation of phospholipase C mediated by platelet thromboxane receptm-s involves a guanine micleotide binding protein-dependent mechanism distinct from that of thrombin. Journal of Clinical Investigation, 79,1269-1275. 

Neubig, R.R. Sklar, L.A. Subsecond modulation of formyl peptide-linked guanine nucleotide-binding proteins by gua-nosine 5 -o-(3-thio)triphosphate in permeabilized neutrophils. Mol. Pharmacol. 1993, 43, 734—740. 

H-ras proteins, the products of the ras onco- and protooncogenes, are guanine nucleotide binding proteins, which act as molecular switch. In the active state, liras proteins are bound to guanosine triphosphate (GTP), and in order to switch to the inactive state, the y-phosphate of the nucleotide has to be hydrolyzed. In the oncogenic mutation, this reaction is suppressed. Understanding this reaction is very important to overcome human cancer, because H-ras proteins frequently mutate to be activated in a variety of human cancer cells [1]. 

Lorenzen, A., Fuss, M., Vogt, H., and Schwabe, U. (1993) Measurement of guanine nucleotide-binding protein activation by A1 adenosine receptor agonists in bovine brain membranes stimulation of guanosine-5 -0-(3-P S]thio)triphosphate binding. Mol. Pharmacol. 44, 115-123. 

Singh AK. 1993. Effects of chronic low-level lead exposure on mRNA expression, ADP-ribosylation and photoaffmity labelling with [ -32P]guanine triphosphate -y -azidoanilide of GTP-binding proteins in neurons isolated from the brain of neonatal and adult rats. Biochem Pharmacol 45 1107-1114. 

When the receptor interacts with its associated G protein, the conformation of the guanine-nucleotide-binding site is altered. The subunits then dissociate, and a phosphatidylinositol-specific phospholipase C (PI-PLC) is activated [5]. The subsequent hydrolysis of phosphatidylinositol bisphosphate then produces inositol triphosphate (IP3) and diacylglycerol (DAG), which are known to be secondary messengers. For example, the water soluble IP3 is released into the cell where its ultimate targets are the calcium storage organelles from which Ca2+ is released [3]. The presence of DAG in cells is known to activate the cellular enzyme protein kinase C (PKC) [6, 7], which phosphorylates a number of cellular... 

Figure 1.10 Model of a G protein-coupled receptor with 7 membrane-spanning domains. Binding of an agonist to the receptor causes GDP to exchange with GTP. The a-GTP complex then dissociates from the receptor and the py complex and interacts with intercellular en mes or ion channels. The Py complex can activate an ion channel or possibly also interact with intercellular enzymes. GDP, guanine diphosphate GTP, guanine triphosphate cAMP, cyclic adenosine monophosphate PKC, protein kinase C PLC, phospholipase C DAG, diacylglycerol.

Blot overlays include the probing of membrane with various molecules to detect the presence of specific binding domains, for example, with guanine triphosphate (25,26) or proteoglycans (27). In the Southern or North Western blotting, the membrane is probed with deoxyribonucleic acid or ribonucleic acid molecules to detect nucleic-acid binding proteins (28). 

N-ras mutation Signal transduction Guanine diphosphate (GDP)/ guanine triphosphate (GTP) binding protein Acute myeloid leukemia, neuroblastoma... 

When a neurotransmitter or hormone binds with its receptor, the a subunit of the G-protein combined with GTP (guanine triphosphate) detaches and activates an effector in the cell (see Figure 3.6). 

G proteins comprise several families of diverse cellular proteins that subserve an equally diverse array of cellular functions. These proteins derive their name from the fact that they bind the guanine nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP) and possess intrinsic GTPase activity. G proteins play a central role in signal transduction as well as in a myriad of cellular processes, including membrane vesicle transport,... 

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