Ligand-dependent serum response factor activation by the human CC chemokine receptors CCR2a and CCR2b is mediated by G proteins of the Gq family
| العنوان: | Ligand-dependent serum response factor activation by the human CC chemokine receptors CCR2a and CCR2b is mediated by G proteins of the Gq family |
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| المؤلفون: | Petra Vatter, Barbara Moepps, Carolin Koenig, Julia Schuhholz, Mariana Pfreimer |
| المصدر: | Journal of Leukocyte Biology. 99:979-991 |
| بيانات النشر: | Oxford University Press (OUP), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Transcriptional Activation, rho GTP-Binding Proteins, 0301 basic medicine, Serum Response Factor, Receptors, CCR2, G protein, Immunology, GTPase, Ligands, Cell Line, 03 medical and health sciences, Chemokine receptor, Heterotrimeric G protein, Chlorocebus aethiops, Serum response factor, Animals, Humans, Protein Isoforms, Immunology and Allergy, Chemokine CCL2, biology, Cell Biology, Cell biology, 030104 developmental biology, Pertussis Toxin, Gq alpha subunit, COS Cells, biology.protein, GTP-Binding Protein alpha Subunits, Gq-G11, Guanine nucleotide exchange factor, CC chemokine receptors |
| الوصف: | Expression of the human CCR2 receptors, CCR2a and CCR2b, in mammalian cells results in ligand-dependent changes in the activity of multiple cellular signal transduction pathways, mediated in most cases by pertussis toxin-sensitive heterotrimeric G proteins of the Gi/o subfamily. In addition, CCR2a and CCR2b receptors have been shown to couple to Gq family members, triggering the canonical activation of phospholipase Cβ isoenzymes. Activation of pertussis toxin-insensitive Gq proteins by cell-surface receptors is not only coupled to activation of phospholipase isoenzymes but also to Rho guanine nucleotide exchange factors, which in turn mediate activation of the Rho GTPases. Activated Rho GTPases regulate numerous cellular functions, including the organization of the actin cytoskeleton and gene transcription, such as the transcription factor serum response factor. These findings prompted us to investigate whether CCR2a and/or CCR2b stimulate serum response factor activity. The results presented herein demonstrate that stimulation of human CCR2a- or CCR2b-expressing COS-7 cells caused a vigorous induction of serum response factor activity. This effect was specifically mediated by Gq and/or G14, as well as Rho A and/or a closely related Rho GTPase. Furthermore, the stimulatory effect of CCR2a and CCR2b and Gαq was sensitive to coexpression of the Gαq-interacting leukemia-associated Rho guanine nucleotide exchange factor. The findings of the work indicate a role for Gαq and/or Gα14 and in CCR2a/CCR2b-stimulated Rho A GTPase-mediated serum response factor activation and introduce a noncanonical pathway activated by CCR2 receptors by coupling to Gq proteins. |
| تدمد: | 1938-3673 0741-5400 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4140e605c1fd3c6c85b64d12152b89b8Test https://doi.org/10.1189/jlb.2ma0815-386rTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4140e605c1fd3c6c85b64d12152b89b8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19383673 07415400 |
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