Journal article
α1-Adrenergic Receptor Signaling via Gh Is Subtype Specific and Independent of Its Transglutaminase Activity
The Journal of biological chemistry, Vol.271(50), pp.32385-32391
12/13/1996
DOI: 10.1074/jbc.271.50.32385
Abstract
Tissue transglutaminase (TGase II) is a Ca2+- and thiol-dependent enzyme that catalyzes the post-translational modification of proteins via the formation of ϵ(γ-glutamyl) lysine bonds. We have shown previously that the GTP-binding protein, Gh, is a TGase II that mediates intracellular signaling by the α1B-adrenergic receptor (AR) (Nakaoka, H., Perez, D. M., Baek, K. J., Das, T., Husain, A., Mison, K., Im, M.-J., and Graham, R. M. (1994) Science 264, 1593-1596). Here, we evaluated the ability of Gh as compared with Gq to mediate receptor-stimulated inositol phosphate turnover by the three α1-subtypes (α1A, α1B, and α1D). In addition, we questioned if the transglutaminase function of Gh is involved in its receptor signaling activity. A mutant form of a human TGase II cDNA in which the codon for the active site cysteine (Cys277) was replaced by serine was cloned into the mammalian expression vector pMT2′. Compared with wild-type TGase II, no transglutaminase activity was observed with transient transfection of this Cys→Ser mutant in COS-1 cells. However, like wild-type TGase, the Cys→Ser mutant mediated receptor-stimulated inositol phosphate turnover when cotransfected with an α1B-AR cDNA. Gαq supported α1-AR-mediated inositol phosphate turnover by all three receptor subtypes. By contrast, although both the wild-type and Cys→Ser construct mediated receptor signaling by the α1B AR and α1D AR, the α1A-AR was unable to interact with Gh. However, a Gh-dependent signaling phenotype could be rescued by a chimeric α1A construct in which the third intracellular loop of the α1A-AR was replaced by that of the α1B-AR. Thus, the signaling function of Gh is independent of its transglutaminase activity and is α1-AR subtype specific. This subtype specificity of the interaction between α1 ARs and Gh involves important determinants in their third intracellular loops.
Details
- Title: Subtitle
- α1-Adrenergic Receptor Signaling via Gh Is Subtype Specific and Independent of Its Transglutaminase Activity
- Creators
- Songhai Chen - University of Iowa, Neuroscience and PharmacologyFang Lin - University of Iowa, Anatomy and Cell BiologySiiri Iismaa - Victor Chang Cardiac Research Institute, St. Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia andKyung N Lee - The Samuel Roberts Noble Foundation, Ardmore, Oklahoma 73401Paul J Birckbichler - The Samuel Roberts Noble Foundation, Ardmore, Oklahoma 73401Robert M Graham - Victor Chang Cardiac Research Institute, St. Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia and
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.271(50), pp.32385-32391
- DOI
- 10.1074/jbc.271.50.32385
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 12/13/1996
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040576102771
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