Abstract：
:Recycling of the majority of agonist-internalized GPCR is dependent on a type I-PDZ "barcode" in their C-tail. The recycling of wild-type (WT) ß1-AR is also dependent on its default "type-1 PDZ barcode", but trafficking of the ß1-AR is inhibited when PKA or its substrate serine at position 312 (Ser312) are inactivated. We tested the hypothesis that phospho-Ser312 provided a second barcode for ß1-AR sorting from endosomes to the plasma membrane by determining the role of retromer/WASH complexes in ß1-AR trafficking. Recycling of WT ß1-AR or WT ß2-AR was dependent on targeting the retromer to endosomal membranes via SNX3 and rab7a, and on complexing the retromer to the WASH pentamer via the C-tail of FAM21 (FAM21C). These maneuvers however, did not inhibit the recycling of a phospho-Ser312 ß1-AR mimic ((S312D) ß1-AR). Knockdown of the trans-acting PDZ protein sorting nexin27 (SNX27) inhibited the recycling of WT ß1-AR and WT ß2-AR, but had no effect on (S312D) ß1-AR∆PDZ or on phosphorylation of WT ß1-AR by PKA at Ser312. However, depletion of FKBP15, a FAM21C-binding endosomal protein, selectively inhibited WT ß1-AR but not ß2-AR recycling, suggesting divergence might exist in GPCR trafficking roadmaps. These results indicate that two barcodes are involved in sorting WT ß1-AR out of early endosomes. The first and antecedent "barcode" was the "type-1 PDZ", followed by a second reversible "phospho-Ser312" verification "barcode". This organization allows tight regulation of ß1-AR density to signaling intensity in conditions associated with aberrant ß1-AR signaling such as in hypertension and heart failure.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Nooh MM,Bahouth SWdoi
10.1016/j.cellsig.2016.10.014subject
Has Abstractpub_date
2017-01-01 00:00:00pages
192-208eissn
0898-6568issn
1873-3913pii
S0898-6568(16)30258-3journal_volume
29pub_type
杂志文章abstract：:This review summarizes some recent findings in human sperm which show that progesterone and 17 alpha hydroxyprogesterone are able rapidly (within seconds) to elevate [Ca2+]i and elicit the acrosome reaction (AR) via a non-genomic cell surface receptor. Progesterone promotes a transient elevation in [Ca2+]i which is bl...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/0898-6568(93)90048-q
更新日期：1993-09-01 00:00:00
abstract：:Clinical studies have elucidated the negative correlation between microtubules-associated protein 1 light chain 3-B (LC3B) protein expression and overall survival of breast cancer patients. Our previous data demonstrated corticortropin-releasing hormone family (CRHs) suppressed migration of breast cancer cells via CRH...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2019.03.001
更新日期：2019-06-01 00:00:00
abstract：:Tribbles 3 homolog (TRB3) is recently identified as a scaffold-like regulator of various signal transducers and has been implicated in several processes including insulin signaling, NF-kappaB signaling, lipid metabolism and BMP signaling. To further understand cellular mechanisms of TRB3 regulation, we performed a yea...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.01.010
更新日期：2008-05-01 00:00:00
abstract：:Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase gene family that contributes to the invasiveness and metastasis in tumor progression. However, the role of LOXL2 in cellular signaling is incompletely understood. In this study, we investigated a possible mechanism of LOXL2 function in tumor metastases in v...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.05.010
更新日期：2014-09-01 00:00:00
abstract：:Previous reports have suggested that the two mitogen-activated protein kinases (MAPKs) in Dictyostelium discoideum, ERK1 and ERK2, can be directly activated in response to external cAMP even though these MAPKs play different roles in the developmental life cycle. To better characterize MAPK regulation, the levels of p...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.10.009
更新日期：2015-01-01 00:00:00
abstract：:Src homology (SH) 3 domains are small modules found in a diverse array of proteins. The presence of an SH3 domain confers upon its resident protein the ability to interact with specific proline-rich sequences in protein binding partners. A major focus of research has highlighted a role for SH3 domain-mediated interact...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(98)00059-x
更新日期：1999-04-01 00:00:00
abstract：:Measurements of prostaglandin E2 (PGE2)-induced adenylyl cyclase activity in membranes isolated from epididymal rat adipocytes revealed inhibition of cAMP production at low concentrations of PGE2 (less than 10 mM) and stimulation at higher concentrations. This biphasic effect of PGE2 was obtained when adenylyl cyclase...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(92)90073-h
更新日期：1992-05-01 00:00:00
abstract：:The adaptor protein Gab-2 coordinates the assembly of the IL-3 signalsome comprising Gab-2, Grb2, Shc, SHP-2 and PI3K. To investigate the role of the pleckstrin homology domain of Gab-2 in this process, epitope-tagged wild type Gab-2 (WTGab-2), Gab-2 lacking its PH domain (DeltaPHGab-2) and the Gab-2 PH domain alone (...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.09.002
更新日期：2006-08-01 00:00:00
abstract：:Macrophages take up oxidized low density lipoprotein (oxLDL) after being exposed to it in the blood vessels. oxLDL transforms macrophages into foam cells, which are a hallmark of atherosclerosis. The effects that oxLDL have on the inflammatory responses of foam cells are not clear. Here, we investigated how oxLDL modu...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.02.001
更新日期：2012-06-01 00:00:00
abstract：:CK1δ and CK1ε are unique in the casein kinase 1 family and play critical roles in a number of physiological intracellular pathways. In particular, these kinases are involved in composing the mammalian circadian clock by phosphorylating core clock proteins. Considering that CK1δ/ε phosphorylate other key biological mol...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2016.12.010
更新日期：2017-02-01 00:00:00
abstract：:13-(S)-Hydroxyoctadecadienoic acid (13-HODE), the lipoxygenase metabolite of linoleic acid, has been shown to reverse the epidermal hyperproliferation induced by topical application of docosahexaenoic acid (DNA, 22:6 n-3) on guinea pig skin. Our initial studies demonstrated that 13-HODE exerts a selective inhibition o...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(97)00099-5
更新日期：1998-02-01 00:00:00
abstract：:The induction of cytolytic activity in PC60, a murine T-cell hybridoma, is paralleled by a rise in the level of BLT-esterase (N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl esterase), a serine esterase specific for activated T-cells. Both interleukin-1 (IL-1) and dibutyryl cAMP were albe to increase the esterase activi...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(90)90045-c
更新日期：1990-01-01 00:00:00
abstract：:The type II epithelial-mesenchymal transition (EMT) produces airway fibrosis and remodeling, contributing to the severity of asthma and chronic obstructive pulmonary disease. While numerous studies have been done on the mechanisms of the transition itself, few studies have investigated the system effects of EMT on sig...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.03.024
更新日期：2015-07-01 00:00:00
abstract：:Cortical and medullary thymocytes can be separated from each other by virtue of the fact that only cortical thymocytes bear peanut agglutinin (PNA) receptors. The mitogenic responses of subpopulations of thymocytes were studied. We have confirmed the results of Conlon et al. [(1982) J. Immun. 128, 797-801], that lecti...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(90)90031-5
更新日期：1990-01-01 00:00:00
abstract：:The Reelin-Disabled 1 (Dab1) signaling pathway plays an important role in neuronal cell migration during brain development. Dab1, an intracellular adapter protein which is tyrosine phosphorylated upon Reelin stimulation, has been directly implicated in the transmission and termination of Reelin-mediated signaling. Two...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.11.007
更新日期：2011-03-01 00:00:00
abstract：:Reelin is a secreted glycoprotein and essential for brain development and plasticity. Recent studies provide evidence that Reelin modifies platelet actin cytoskeletal dynamics. In this study we sought to dissect the contribution of Reelin in arterial thrombus formation. Here we analyzed the impact of Reelin in arteria...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2017.09.016
更新日期：2017-12-01 00:00:00
abstract：:The heptahelical AT(1) G-protein-coupled receptor lacks inherent tyrosine kinase activity. Angiotensin II binding to AT(1) nevertheless activates several tyrosine kinases and stimulates both tyrosine phosphorylation and phosphatase activity of the SHP-2 tyrosine phosphatase in vascular smooth muscle cells. Since a bal...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2003.08.001
更新日期：2004-03-01 00:00:00
abstract：:Cannabinoids exert a variety of physiological and pharmacological responses in humans through interaction with specific cannabinoid receptors. Cannabinoid receptors described to date belong to the seven-transmembrane-domain receptor superfamily and are coupled through the inhibitory G(i) protein to adenylyl cyclase in...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(03)00036-6
更新日期：2003-09-01 00:00:00
abstract：:Akt (also known as protein kinase B or PKB) comprises three closely related isoforms Akt1, Akt2 and Akt3 (or PKBα/β/γ respectively). We have a very good understanding of the mechanisms by which Akt isoforms are activated by growth factors and other extracellular stimuli as well as by oncogenic mutations in key upstrea...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2011.05.004
更新日期：2011-10-01 00:00:00
abstract：:The interferon regulated transcription factor IRF-1 is a tumour suppressor protein that is activated in response to viral infection and cell signalling activated by double stranded DNA lesions. IRF-1 has a short half-life (t(0.5) 20-40 min) allowing rapid changes in steady state levels by modulating its rate of degrad...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.05.004
更新日期：2009-10-01 00:00:00
abstract：:Signaling co-receptors are diverse, multifunctional components of most major signaling pathways, with roles in mediating and regulating signaling in both physiological and pathophysiological circumstances. Many of these signaling co-receptors, including CD44, glypicans, neuropilins, syndecans and TssRIII/betaglycan ar...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2009.05.001
更新日期：2009-11-01 00:00:00
abstract：:Synthesis and degradation of lipids in mammalian adipocytes are tightly and coordinatedly regulated by insulin, fatty acids, reactive oxygen species and drugs. Conversely, the lipogenic or lipolytic state of adipocytes is communicated to other tissues by the secretion of soluble adipocytokines. Here we report that ins...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.10.021
更新日期：2009-02-01 00:00:00
abstract：:We have previously shown that N18TG2 neuroblastoma cells express the type 6 adenylyl cyclase and that preincubation with nitric oxide (NO) attenuates Gs- and forskolin-stimulated activity. Here we show that this inhibition reflects a direct action of NO on the adenylyl cyclase. Preincubation of N18TG2 cell membranes a...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(99)00082-0
更新日期：2000-04-01 00:00:00
abstract：:The small GTPase Rac1 plays a pivotal role in insulin-stimulated glucose uptake in skeletal muscle, which is mediated by GLUT4 translocation to the plasma membrane. However, regulatory mechanisms for Rac1 and its role in the signaling pathway composed of phosphoinositide 3-kinase and the serine/threonine kinase Akt re...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.02.023
更新日期：2013-06-01 00:00:00
abstract：:Agonist stimulation of G-protein coupled receptors (GPCRs) results in the redistribution of the receptor from the cell surface into intracellular compartments through the process of endocytosis. Monitoring ligand-mediated internalization of GPCRs in living cells has become experimentally accessible by applying fluores...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.05.017
更新日期：2008-10-01 00:00:00
abstract：:The present study has examined the effects of adenosine A1 receptors on second messenger processes in GH3 cells. A1 receptors are present which are shown to inhibit adenylate cyclase in a GTP-requiring manner. Hormone (VIP) stimulation is also absolutely required for the observation of inhibition. Adenosine A1 recepto...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(89)90023-5
更新日期：1989-01-01 00:00:00
abstract：:In this work, we used colon carcinoma cell-line HCT116 to study the involvement of the 86-kDa subunit (Ku86) of DNA-protein kinase (DNA-PK) in human tumoural cell proliferation. We transfected these cells with a 639-bp cDNA encoding a Ku86 portion inserted into pcDNA3.1 vector in the antisense orientation. After selec...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(00)00126-1
更新日期：2000-12-01 00:00:00
abstract：:p21(Waf1/Cip1/Sdi1) was originally identified as an inhibitor of cyclin-dependent kinases, a mediator of p53 in growth suppression and a marker of cellular senescence. p21 is required for proper cell cycle progression and plays a role in cell death, DNA repair, senescence and aging, and induced pluripotent stem cell r...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2010.01.013
更新日期：2010-07-01 00:00:00
abstract：:SHP1 and SHP2 tyrosine phosphatases have both been implicated in signalling pathways downstream of the interleukin-3 (IL-3) receptor. We have investigated the co-association of SHP1 and SHP2 with tyrosine-phosphorylated proteins in IL-3-dependent BaF/3 cells. We demonstrate that both SHP1 and SHP2 associate with Aic2A...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(01)00241-8
更新日期：2002-03-01 00:00:00
abstract：:In extracts of human platelets, three isoenzymes of cyclic nucleotide phosphodiesterase (PDE), namely, PDE2, PDE3, and PDE5, were identified; activities of PDE1 and PDE4 were not detected. In human platelets, the cGMP-hydrolytic activity was about six times higher than the cAMP-hydrolytic activity, and PDE5 and PDE3 a...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(96)00112-x
更新日期：1996-12-01 00:00:00
