Abstract:
:Timeless was originally identified in Drosophila as an essential component of circadian cycle regulation, where its function is tightly controlled at the protein level by tyrosine phosphorylation and subsequent degradation. In mammals, Timeless has also been implicated in circadian rhythms as well as cell cycle control and embryonic development. Here we report that mammalian Timeless is an SH3 domain-binding protein and substrate for several members of the Src protein-tyrosine kinase family, including Fyn, Hck, c-Src and c-Yes. Co-expression of Tim with Fyn or Hck was followed by ubiquitylation and subsequent degradation in human 293T cells. While c-Src and c-Yes also promoted Tim ubiquitylation, in this case ubiquitylation correlated with Tim protein accumulation rather than degradation. Both c-Src and c-Yes selectively promoted modification of Tim through Lys63-linked polyubiquitin, which may explain the differential effects on Tim protein turnover. These data show distinct and opposing roles for individual Src-family members in the regulation of Tim protein levels, suggesting a unique mechanism for the regulation of Tim function in mammals.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
O'Reilly LP,Zhang X,Smithgall TEdoi
10.1016/j.cellsig.2012.12.009subject
Has Abstractpub_date
2013-04-01 00:00:00pages
860-6issue
4eissn
0898-6568issn
1873-3913pii
S0898-6568(12)00346-4journal_volume
25pub_type
杂志文章abstract::The ubiquitously expressed phosphoinositide 3-kinase (PI3K) family of lipid kinases control diverse cellular functions including cell survival, proliferation, metabolism and migration. Class I PI3Ks generate two distinct 3-phosphoinositide lipid messengers, PI(3,4,5)P3 (PIP3) and PI(3,4)P2, that recruit signaling effe...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2015.05.013
更新日期:2015-09-01 00:00:00
abstract::We report on a novel method to monitor changes in intracellular cAMP concentration ([cAMP]i) within intact living cells using a chimeric fusion of the catalytic subunit of cAMP-dependent protein kinase to green fluorescent protein (PKAcat-GFP). In stably transfected unstimulated fibroblasts, fusion protein fluorescenc...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.01.006
更新日期:2004-08-01 00:00:00
abstract::The possible involvement of zeta isozyme of protein kinase C (PKC zeta) in phorbol ester-induced signal transduction was investigated in mouse epidermal cells. Western blot analysis of RESOURCE Q column chromatography eluates obtained from 105,000 g supernatants and particulate fractions of epidermal cells was perform...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(95)00019-l
更新日期:1995-07-01 00:00:00
abstract::Prostatic stromal proliferation may be commonly associated with the development of benign prostatic hyperplasia. In this study, we investigate the role of testosterone and protein kinase C in stimulating cultured stromal cell proliferation. Testosterone increased the uptake of [(3)H]-thymidine into the human cultured ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00205-4
更新日期:2001-10-01 00:00:00
abstract::Lithium is an anti-depressant drug that also possesses immunomodulatory functions. The anti-inflammatory effect of lithium is thought to involve activation of the transcription factor CREB, although the underlying mechanism is incompletely understood. We show here that in macrophages lithium stimulates Tpl2, a MAP kin...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.12.010
更新日期:2009-04-01 00:00:00
abstract::β-Adrenergic receptors (βAR) and D(2)-like dopamine receptors (which include D(2)-, D(3)- and D(4)-dopamine receptors) activate G(s) and G(i), the stimulatory and inhibitory heterotrimeric G proteins, respectively, which in turn regulate the activity of adenylyl cyclase (AC). β(2)-Adrenergic receptors (β(2)AR) and D(4...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.06.011
更新日期:2012-11-01 00:00:00
abstract::The duration of ERK1/2 activation influences the nature of the biological response to agonist. Members of the AP-1 transcription factor family are well known targets of the ERK1/2 pathway and are expressed in a temporally coordinated fashion during cell cycle re-entry. In CCl39 fibroblasts, sustained ERK1/2 activation...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2006.09.001
更新日期:2007-04-01 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 mammalian target of rapamycin complex 1(mTORC1) integrates diverse signals to control cell growth, proliferation, survival, and metabolism. Role of reactive oxygen species (ROS) on mTORC1 signaling remains obscure and mechanisms through which ROS modulate mTORC1 are not known.We demonstrate that low doses ROS expo...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.05.015
更新日期:2010-10-01 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::Exponentially growing V79 Chinese hamster lung fibroblasts irradiated with 7 Gy X-rays undergo cell cycle arrest in the S and G2 phases. These arrests are released, probably on completion of DNA repair. A premature release occurs after treatment of irradiated cells with caffeine. This release is accompanied by increas...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(94)90008-6
更新日期:1994-07-01 00:00:00
abstract::The activation of corticotrophin-releasing hormone receptor (CRHR) 1 is implicated in neuronal injury in experimental stroke. However, little is known about the relationship between CRHR1 activation and brain endothelial barrier impairment after ischemia and reperfusion (I/R). Recently we have demonstrated that the ac...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109467
更新日期:2020-02-01 00:00:00
abstract::The effects of estrogen in breast epithelial cells are mediated primarily via estrogen receptor alpha and estrogen receptor beta (ERalpha and ERbeta). Accumulating evidence implicates a role for Ca2+ and calmodulin in breast carcinoma, as well as in the function of ERalpha. Calmodulin contributes to the regulation of ...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2006.08.018
更新日期:2007-03-01 00:00:00
abstract::Reactive Oxygen Species (ROS) are crucial to multiple biological processes involved in the pathophysiology of inflammation, and are also involved in redox signaling responses. Although previous reports have described an association between oxidative events and the modulation of innate immunity, a role for redox signal...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.12.014
更新日期:2015-04-01 00:00:00
abstract::Janus kinase 2 (Jak2) has a pivotal role in erythropoietin (Epo) signaling pathway, including erythrocyte differentiation and Stat5 activation. In the course of screening for critical phosphorylation of tyrosine residues in Jak2, we identified tyrosine 913 (Y(913)) as a novel and functional phosphorylation site, which...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.07.008
更新日期:2008-11-01 00:00:00
abstract::C5L2 is a receptor that binds to C5a and belongs to the family of G protein-coupled receptors, but its role in physiological C5a-mediated responses remains under debate. Here we show that, like the canonical C5a receptor C5aR, C5L2 plays a pro-inflammatory role in a murine model of acute experimental colitis. We demon...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.02.021
更新日期:2014-07-01 00:00:00
abstract::The human NPY Y(1) receptor undergoes fast agonist-induced internalization via clathrin-coated pits then recycles back to the cell membrane. In an attempt to identify the molecular determinants involved in this process, we studied several C-terminal truncation mutants tagged with EFGP. In the absence of agonist, Y(1) ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.09.007
更新日期:2011-01-01 00:00:00
abstract::Recent reports show that protein kinase A (PKA), but not exchange protein activated by cAMP (EPAC), acts in a cell autonomous manner to constitutively reduce the angiogenic sprouting capacity of murine and human endothelial cells. Specificity in the cellular actions of individual cAMP-effectors can be achieved when a ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.06.007
更新日期:2019-10-01 00:00:00
abstract::We demonstrate the difference between the follistatin isoforms (FS-288 and FS-315), two activin-binding proteins, in the neutralizing activity for activin signalling. Transcriptional reporter assay using 3TP-Lux, an activin-responsive reporter construct, showed that the inhibitory effect of FS-288 on activin-induced t...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(00)00099-1
更新日期:2000-08-01 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::We found that CKD712, an S enantiomer of YS49, strongly inhibited inducible nitric oxide synthase (iNOS) and NO induction but showed a weak inhibitory effect on cyclooxygenase-2 (COX-2) and PGE(2) induction in LPS-stimulated RAW 264.7 cells. We, therefore, investigated the molecular mechanism(s) responsible for this b...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.06.012
更新日期:2008-10-01 00:00:00
abstract::The D405N and Y546F mutations of the human lutropin receptor (hLHR) have previously been shown to partially attenuate hCG-stimulated cAMP synthesis despite normal cell surface expression and hCG binding affinity (Min, L. and Ascoli, M. Mol. Endocrinol. 14:1797-1810, 2000). We now show that these mutations each stabili...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.07.003
更新日期:2009-11-01 00:00:00
abstract::Understanding receptor activation is important for disease intervention. Activation of the receptor tyrosine kinase c-KIT is involved in numerous diseases including melanoma, mastocytosis, multiple myeloma and gastrointestinal stromal tumors. To better understand the regulation of activation, we studied the two c-KIT ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.07.011
更新日期:2013-11-01 00:00:00
abstract::Beta-adrenergic, alpha-1-adrenergic and glucagon stimulation of glucose release were compared between hepatocytes which were freshly isolated, incubated for 3 h in suspension or cultivated for 4 or 24 h in plastic culture flasks in the presence and absence of the protein kinase C activator 12-O-tetradecanoylphorbol-13...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(92)90051-9
更新日期:1992-11-01 00:00:00
abstract::In humans, thromboxane (TX) A₂ signals through the TPα and TPβ isoforms of its G-protein coupled TXA₂ receptor (TP) to mediate a host of (patho)physiologic responses. Herein, angio-associated migratory cell protein (AAMP) was identified as a novel interacting partner of both TPα and TPβ through an interaction dependen...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.12.003
更新日期:2011-04-01 00:00:00
abstract::Endogenous reactive oxygen species (ROS) control is important for the maintenance of self-renewal of embryonic stem (ES) cells. Although miRNAs have been found to be critically involved in the regulation of the self-renewal, whether miRNAs can regulate the signaling axis to control ROS in ES cells is unclear. Here we ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.03.010
更新日期:2014-07-01 00:00:00
abstract::Overcoming de novo and acquired resistance to anticancer drugs that target signaling networks is a formidable challenge for drug design and effective cancer therapy. Understanding the mechanisms by which this resistance arises may offer a route to addressing the insensitivity of signaling networks to drug intervention...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.10.011
更新日期:2011-02-01 00:00:00
abstract::We have isolated a cDNA from a human liver library which is 2349 base pairs in length and encodes a near-full length seven transmembrane receptor (432 amino acids), 85% homologous to the amino acid sequence for the rat vasoactive intestinal peptide (VIP) receptor. Northern blot analysis identifies a major species at 3...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(94)90037-x
更新日期:1994-03-01 00:00:00
abstract::The Integrin-mediated cell adhesion to the extracellular matrix is implicated in the control of proliferation, survival, migration and differentiation of myoblasts. Focal adhesion kinase (FAK) mediates signals from Integrins and plays an essential role in myotube formation. Cdo forms a multiprotein complex that includ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.03.001
更新日期:2011-07-01 00:00:00
abstract::Ubiquitination controls multiple cellular processes relevant to cancer pathogenesis. Using Gene Set Enrichment Analysis of an mRNA transcriptome dataset, we have identified genes encoding components of the ubiquitin system that are differentially expressed in colorectal cancers as compared to normal colonic mucosa. Am...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.08.012
更新日期:2013-01-01 00:00:00