| 1. |
- Araç, Demet, et al.
(författare)
-
Dissecting signaling and functions of adhesion G protein-coupled receptors
- 2012
-
Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1276:1, s. 1-25
-
Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) comprise an expanded superfamily of receptors in the human genome. Adhesion class G protein-coupled receptors (adhesion-GPCRs) form the second largest class of GPCRs. Despite the abundance, size, molecular structure, and functions in facilitating cell and matrix contacts in a variety of organ systems, adhesion-GPCRs are by far the most poorly understood GPCR class. Adhesion-GPCRs possess a unique molecular structure, with extended N-termini containing various adhesion domains. In addition, many adhesion-GPCRs are autoproteolytically cleaved into an N-terminal fragment (NTF, NT, α-subunit) and C-terminal fragment (CTF, CT, β-subunit) at a conserved GPCR autoproteolysis-inducing (GAIN) domain that contains a GPCR proteolysis site (GPS). These two features distinguish adhesion-GPCRs from other GPCR classes. Though active research on adhesion-GPCRs in diverse areas, such as immunity, neuroscience, and development and tumor biology has been intensified in the recent years, the general biological and pharmacological properties of adhesion-GPCRs are not well known, and they have not yet been used for biomedical purposes. The "6th International Adhesion-GPCR Workshop," held at the Institute of Physiology of the University of Würzburg on September 6-8, 2012, assembled a majority of the investigators currently actively pursuing research on adhesion-GPCRs, including scientists from laboratories in Europe, the United States, and Asia. The meeting featured the nascent mechanistic understanding of the molecular events driving the signal transduction of adhesion-GPCRs, novel models to evaluate their functions, and evidence for their involvement in human disease.
|
|
| 2. |
- Liebscher, Ines, et al.
(författare)
-
New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors
- 2014
-
Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1333, s. 43-64
-
Tidskriftsartikel (refereegranskat)abstract
- The class of adhesion G protein-coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven-transmembrane α-helix-a structural feature of all GPCRs-the class of aGPCRs is characterized by the presence of a large N-terminal extracellular region. In addition, all aGPCRs but one (GPR123) contain a GPCR autoproteolysis-inducing (GAIN) domain that mediates autoproteolytic cleavage at the GPCR autoproteolysis site motif to generate N- and a C-terminal fragments (NTF and CTF, respectively) during protein maturation. Subsequently, the NTF and CTF are associated noncovalently as a heterodimer at the plasma membrane. While the biological function of the GAIN domain-mediated autocleavage is not fully understood, mounting evidence suggests that the NTF and CTF possess distinct biological activities in addition to their function as a receptor unit. We discuss recent advances in understanding the biological functions, signaling mechanisms, and disease associations of the aGPCRs.
|
|
| 3. |
- Tabar, Laszlo, et al.
(författare)
-
Swedish Two-County Trial: Impact of Mammographic Screening on Breast Cancer Mortality during 3 Decades
- 2011
-
Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 0033-8419 .- 1527-1315. ; 260:3, s. 658-663
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To estimate the long-term (29-year) effect of mammographic screening on breast cancer mortality in terms of both relative and absolute effects. less thanbrgreater than less thanbrgreater thanMaterials and Methods: This study was carried out under the auspices of the Swedish National Board of Health and Welfare. The board determined that, because randomization was at a community level and was to invitation to screening, informed verbal consent could be given by the participants when they attended the screening examination. A total of 133 065 women aged 40-74 years residing in two Swedish counties were randomized into a group invited to mammographic screening and a control group receiving usual care. Case status and cause of death were determined by the local trial end point committees and, independently, by an external committee. Mortality analysis was performed by using negative binomial regression. less thanbrgreater than less thanbrgreater thanResults: There was a highly significant reduction in breast cancer mortality in women invited to screening according to both local end point committee data (relative risk [RR] = 0.69; 95% confi dence interval: 0.56, 0.84; P andlt;.0001) and consensus data (RR = 0.73; 95% confi dence interval: 0.59, 0.89; P =.002). At 29 years of follow-up, the number of women needed to undergo screening for 7 years to prevent one breast cancer death was 414 according to local data and 519 according to consensus data. Most prevented breast cancer deaths would have occurred (in the absence of screening) after the first 10 years of follow-up. less thanbrgreater than less thanbrgreater thanConclusion: Invitation to mammographic screening results in a highly significant decrease in breast cancer-specific mortality. Evaluation of the full impact of screening, in particular estimates of absolute benefit and number needed to screen, requires follow-up times exceeding 20 years because the observed number of breast cancer deaths prevented increases with increasing time of follow-up.
|
|
