scholarly journals Synthetic alpha-thrombin receptor peptides activate G protein-coupled signaling pathways but are unable to induce mitogenesis.

1992 ◽  
Vol 3 (1) ◽  
pp. 95-102 ◽  
Author(s):  
V Vouret-Craviari ◽  
E Van Obberghen-Schilling ◽  
U B Rasmussen ◽  
A Pavirani ◽  
J P Lecocq ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Phospholipase C ◽  
G Protein ◽  
Synthetic Peptides ◽  
Cleavage Site ◽  
Amino Acid Sequences ◽  
Thrombin Receptor ◽  
Thrombin Cleavage ◽  
Ccl39 Cells ◽  
G Protein Coupled

alpha-Thrombin (thrombin) stimulates phospholipase C and modulates the activity of adenylate cyclase in a number of cell types via G protein-coupled receptors. It is also a potent growth factor, notably for a line of hamster fibroblasts (CCL39 cells). Recently, predicted amino acid sequences for human and hamster thrombin receptors have been reported that display a putative thrombin cleavage site in the N-terminal extracellular domain. Synthetic peptides corresponding to 14 residues carboxyl to the presumed thrombin cleavage site of the human receptor have been shown to activate platelets as well as the thrombin receptor expressed in Xenopus oocytes. In the present study we have examined the effects of synthetic peptides corresponding to the same region of the hamster receptor (S-42-L-55) and shorter peptides (2-7 residues) on signal transducing systems in CCL39 cells. Our results indicate that hamster receptor peptides of greater than or equal to 5 residues effectively stimulate phospholipase C in CCL39 cells via the thrombin receptor and induce rapid desensitization of the response. The same peptides also inhibit adenylate cyclase in a pertussis toxin-sensitive manner. Although the peptides are potent agonists of serotonin release in platelets, unlike thrombin, by themselves they are not mitogenic. However, they potentiate DNA synthesis in cooperation with growth factors possessing tyrosine kinase receptors. Hence, we conclude that the potent mitogenic action of thrombin cannot be accounted for solely by the activation of the cloned receptor. We postulate the existence of an additional receptor activated by thrombin, which is required for its full mitogenic potential.

scholarly journals IMMUNOLOGICAL INVESTIGATIONS OF HHV-6 U12 AND U51 ENCODED PROTEINS INVOLVEMENT IN AUTOIMMUNE THYROIDITIS DEVELOPMENT

2020 ◽  
Author(s):  
Alina Sultanova ◽  
Maksims Cistjakovs ◽  
Liba Sokolovska ◽  
Egils Cunskis ◽  
Modra Murovska
Keyword(s):  
Amino Acid ◽  
G Protein ◽  
Autoimmune Thyroiditis ◽  
Synthetic Peptides ◽  
Human Herpesvirus ◽  
Amino Acid Sequences ◽  
G Protein Coupled Receptors ◽  
Igm Antibodies ◽  
Specific Igg ◽  
G Protein Coupled

AbstractHuman herpesvirus 6 (HHV-6) is a human pathogen with a wide cell tropism and many immunomodulating properties. HHV-6 has been linked to the development of multiple diseases, among them – autoimmune. Conflicting evidence implicates HHV-6 in autoimmune thyroiditis (AIT). HHV-6 contains two genes (U12 and U51) that encode putative homologues of human G-protein-coupled receptors (GPCR) like CCR1, CCR3 and CCR5. It has been shown that proteins encoded by HHV-6 U12 and U51 genes can be expressed on the surface of epithelial and some peripheral blood mononuclear cells populations, which makes them a potential cause for evoking autoimmunity.The aim of this study was to identify potentially immunogenic synthetic peptides derived from HHV-6 U12 and U51 amino acid sequences and to find evidences of the possible involvement of these proteins in AIT development. 62 AIT patients positive for HHV-6 infection were enrolled in this study. 30 different synthetic peptides designed from HHV-6 U12 and U51 proteins’ amino acid sequences, as well as, recombinant human CCR1, CCR3 and CCR5 proteins were used for suspension multiplex immunological assay (SMIA) to detect specific IgG, and IgM antibodies.HHV-6 peptide specific IgG and IgM antibodies were found in patient’s samples, with higher signals for IgM antibodies, which is indicative of reactivation and active HHV-6 infection. As well recombinant CCR1 and CCR5 showed high signals on IgM antibodies which is indicating on the presence of potential auto-antibodies against human G protein-coupled receptors. No cross reactivity between HHV-6 peptide specific antibodies and human recombinant CCR1, CCR3 and CCR5 was found, however, the possibility of cross-reactive autoantibodies specific for structural epitopes cannot be excluded.

scholarly journals Activation of Src family kinase activity by the G protein-coupled thrombin receptor in growth-responsive fibroblasts.

1994 ◽  
Vol 269 (44) ◽  
pp. 27372-27377
Author(s):  
Y H Chen ◽  
J Pouysségur ◽  
S A Courtneidge ◽  
E Van Obberghen-Schilling
Keyword(s):  
G Protein ◽  
Kinase Activity ◽  
Thrombin Receptor ◽  
Src Family Kinase ◽  
G Protein Coupled

scholarly journals Dual coupling of the α-thrombin receptor to signal-transduction pathways involving phosphatidylinositol and phosphatidylcholine metabolism

1998 ◽  
Vol 337 (1) ◽  
pp. 97-104 ◽  
Author(s):  
Jie CHENG ◽  
Joseph J. BALDASSARE ◽  
Daniel M. RABEN
Keyword(s):  
Signal Transduction ◽  
Cleavage Site ◽  
Thrombin Receptor ◽  
Signal Transduction Pathways ◽  
Metabolizing Enzymes ◽  
Thrombin Cleavage ◽  
Messenger Molecules ◽  
Mitogenic Signalling ◽  
Signalling Cascade ◽  
Phosphatidylcholine Metabolism

Addition of α-thrombin to quiescent IIC9 cells results in the activation of lipid-metabolizing enzymes associated with signal-transduction cascades. These enzymes include phosphatidylinositol (PI)-specific phospholipase C (PI-PLC), phosphatidylcholine (PC)-specific phospholipases C and D and phospholipase A2 (PLA2). Whereas the α-thrombin receptor has been shown to couple with PI-PLCs, it is not clear whether this receptor, or a putative second receptor, couples to one or more of the other phospholipases. In this report we determine whether the cloned receptor couples to all or a subset of these enzymes. We show that (i) an α-thrombin-receptor-activating peptide also elicits the above responses and (ii) addition of enterokinase to IIC9 cells, stably transfected with an α-thrombin receptor (enterokinase- responsive α-thrombin receptor, EKTR) containing an enterokinase cleavage site in place of an α-thrombin cleavage site, stimulates both PI and PC hydrolysis, including PLA2. Enterokinase also induces mitogenesis in the IIC9s transfected with EKTR. These results indicate that, in addition to initiating a mitogenic signalling cascade, the cloned α-thrombin receptor couples to enzymes involved in generating PC-derived, as well as PI-derived, second-messenger molecules in IIC9s. Additionally, using the cells transfected with EKTR, we further demonstrate that only activated, i.e. cleaved, receptors are desensitized.

scholarly journals Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1

1998 ◽  
Vol 330 (2) ◽  
pp. 605-609 ◽  
Author(s):  
C. M. Gerben ZONDAG ◽  
R. Friso POSTMA ◽  
Ingrid VAN ETTEN ◽  
Ingrid VERLAAN ◽  
H. Wouter MOOLENAAR
Keyword(s):  
Adenylate Cyclase ◽  
Map Kinase ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Lpa Receptor ◽  
Kinase Activation ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are structurally related lipid mediators that act on distinct G-protein-coupled receptors to evoke similar responses, including Ca2+ mobilization, adenylate cyclase inhibition, and mitogen-activated protein (MAP) kinase activation. However, little is still known about the respective receptors. A recently cloned putative LPA receptor (Vzg-1/Edg-2) is similar to an orphan Gi-coupled receptor termed Edg-1. Here we show that expression of Edg-1 in Sf9 and COS-7 cells results in inhibition of adenylate cyclase and activation of MAP kinase (Gi-mediated), but not Ca2+ mobilization, in response to S1P. These responses are specific in that (i) S1P action is not mimicked by LPA, and (ii) Vzg-1/Edg-2 cannot substitute for Edg-1. Thus the Edg-1 receptor is capable of mediating a subset of the cellular responses to S1P.

scholarly journals Cell Density Sensing Mediated by a G Protein-coupled Receptor Activating Phospholipase C

1998 ◽  
Vol 273 (14) ◽  
pp. 8161-8168 ◽  
Author(s):  
Derrick T. Brazill ◽  
David F. Lindsey ◽  
John D. Bishop ◽  
Richard H. Gomer
Keyword(s):  
Phospholipase C ◽  
G Protein ◽  
Cell Density ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Shc adaptor proteins are key transducers of mitogenic signaling mediated by the G protein-coupled thrombin receptor.

1996 ◽  
Vol 15 (5) ◽  
pp. 1037-1044 ◽  
Author(s):  
Y. Chen ◽  
D. Grall ◽  
A. E. Salcini ◽  
P. G. Pelicci ◽  
J. Pouysségur ◽  
...  
Keyword(s):  
G Protein ◽  
Adaptor Proteins ◽  
Thrombin Receptor ◽  
Mitogenic Signaling ◽  
G Protein Coupled

Dual Regulation of Phospolipase C Activity by G Proteins

Physiology ◽  
1993 ◽  
Vol 8 (2) ◽  
pp. 61-63
Author(s):  
H Deckmyn ◽  
C Van Geet ◽  
J Vermylen
Keyword(s):  
Adenylate Cyclase ◽  
Phospholipase C ◽  
G Protein ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Inhibitory Pathway ◽  
Close Parallelism

Some subtypes of phosphatidylinositide-specific phospholipase C (PLC) are activated via pertussis toxin-sensitive or -insensitive G proteins. However, a G protein-dependent PLC inhibitory pathway also may exist. The resultant picture is of dual regulation of PLC, showing a close parallelism with the dual regulation of adenylate cyclase.

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