Abstract:
:SCF induces autophosphorylation of Kit and activates a variety of signaling components including Jnks, Erks, PI 3 Kinase, the JAK-Stat pathway and members of the Src family. Previously we showed that Lyn is activated at multiple points during SCF-induced cell cycle progression and contributes to SCF-mediated growth, chemotaxis and internalization of Kit. However, the Kit-dependent biochemical events that require Lyn are unknown. In this study, we used Lyn-deficient bone marrow mast cells (BMMC) to examine the contribution of this Src family member to tyrosine phosphorylation of Kit and SCF-induced activation of Jnks, Akt, Stat3 and Erks. Although surface expression of Kit was increased in Lyn-deficient BMMC, SCF-induced phosphorylation and growth was reduced compared to wild-type BMMC. Downstream of Kit, SCF-induced activation of Jnks was markedly reduced in Lyn-deficient BMMC. Further, Lyn was required for SCF-induced tyrosine phosphorylation of Stat3. Interestingly, Kit was constitutively associated with PI 3 Kinase in Lyn-deficient BMMC and this correlated with constitutive phosphorylation of Akt. This was in marked contrast to wild-type BMMC, where both these events were induced by SCF. These data indicate that in BMMC, Lyn contributes to SCF-induced phosphorylation of Kit, as well as phosphorylation of Jnks and Stat3. In contrast, Lyn may negatively regulate the PI 3 Kinase/Akt pathway. The opposing effects of Lyn on these signaling pathways may explain the pleiotropic effects ascribed to this Src family member in the literature.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Shivakrupa R,Linnekin Ddoi
10.1016/j.cellsig.2004.06.004subject
Has Abstractpub_date
2005-01-01 00:00:00pages
103-9issue
1eissn
0898-6568issn
1873-3913pii
S0898656804001226journal_volume
17pub_type
杂志文章abstract::ASB proteins are the specificity subunits of cullin5-RING E3 ubiquitin ligases (CRL5) that play roles in ubiquitin-mediated protein degradation. However, how their activity is regulated remains poorly understood. Here, we unravel a novel mechanism of regulation of a CRL5 through phosphorylation of its specificity subu...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.09.011
更新日期:2013-12-01 00:00:00
abstract::Non-alcoholic fatty liver disease is the most commonly occurring chronic liver disease, and hepatic steatosis, a condition defined as extensive lipid accumulation in hepatocytes, is associated with liver dysfunction and metabolic diseases, such as, obesity and type II diabetes. Apelin is an adipokine that acts on a G ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2017.08.003
更新日期:2017-11-01 00:00:00
abstract::Ceramide 1-phosphate (C1P) is a bioactive sphingolipid that is implicated in the regulation of cell homeostasis and the control of inflammation. It is mitogenic for fibroblasts and macrophages, and has been described as potent inhibitor of apoptosis. Using RAW 264.7 macrophages we have now discovered a new biological ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.11.003
更新日期:2009-03-01 00:00:00
abstract::Extracellular adenine dinucleotides are modulators of blood vessel tone. We have previously demonstrated that Ap(2)A and Ap(4)A induce the synthesis of nitric oxide (NO) from bovine aortic endothelial cells (BAEC) while Ap(3)A and Ap(5)A do not [FEBS Lett. 427 (1998) 320; Arch. Biochem. Biophys. 364 (1999) 280.]. In t...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(00)00147-9
更新日期:2001-02-01 00:00:00
abstract::CyrA is a novel cysteine-rich protein with four EGFL repeats that was isolated using the calmodulin (CaM) binding overlay technique (CaMBOT), suggesting it is a CaM-binding protein (CaMBP). The full-length 63kDa cyrA is cleaved into two major C-terminal fragments, cyrA-C45 and cyrA-C40. A putative CaM-binding domain w...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.03.008
更新日期:2011-07-01 00:00:00
abstract::Pancreatic fibrosis, a key feature of chronic pancreatitis and pancreatic cancer, is mediated by activated pancreatic stellate cells (PSC). Connective tissue growth factor (CTGF) has been suggested to play a major role in fibrogenesis by enhancing PSC activation after binding to alpha5beta1 integrin. Here, we have foc...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.06.016
更新日期:2008-10-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(99)00030-3
更新日期:1999-08-01 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::High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic cancer. Emerging evidence suggests that tumor-associated macrophages (TAMs) play an immunosuppressive role in the tumor microenvironment and promote tumor growth, angiogenesis, and metastasis in ovarian cancer. Therefore, targeting TAMs in pati...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109539
更新日期:2020-04-01 00:00:00
abstract::Targeted therapy is becoming the mainstay of cancer treatment due to reduced side effects and enhanced tumor attack. In the last few decades, Murine Double Minute 2 (MDM2) protein has become one of the targets for developing cancer therapies. Blocking MDM2-p53 interaction has long been considered to offer a broad rang...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109742
更新日期:2020-11-01 00:00:00
abstract::Obesity is a widespread health problem that brings about various adipose tissue dysfunctions. The balance of energy storage and energy expenditure is critical for normal fat accumulation and lipid metabolism. Therefore, understanding the molecular basis of adipogenesis and thermogenesis is essential to maintain adipos...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2018.07.012
更新日期:2018-11-01 00:00:00
abstract::Both type I interferons (IFNs) and interferon regulatory factors (IRFs) are well characterized in viral infections, whereas they are far less studied in bacterially activated toll-like receptor (TLR) pathways. Here, we studied the involvement of IRF1 and IRF2 in TLR2-mediated responses. In mouse macrophages, IRF2 was ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.06.017
更新日期:2008-10-01 00:00:00
abstract::Transforming growth factor-β (TGF-β) signaling plays a key role in regulating normal cell growth and differentiation, and mutations affecting members of this pathway contribute to cancer development and metastasis. In DNA mismatch repair (MMR)-deficient colorectal cancers that exhibit the microsatellite instability (M...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.04.012
更新日期:2016-08-01 00:00:00
abstract::The p75 neurotrophin receptor (p75(NTR)) plays a critical role in various neuronal and non-neuronal cell types by regulating cell survival, differentiation and proliferation. To evaluate the influence of p75(NTR) in breast cancer development, we have established and characterized breast cancer cells which stably overe...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.07.014
更新日期:2010-12-01 00:00:00
abstract::HOX family transcription factors belong to a highly conserved subgroup of the homeobox superfamily that determines cellular fates in embryonic morphogenesis and the maintenance of adult tissue architecture. HOX family transcription factors play key roles in numerous cellular processes including cell growth, differenti...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2019.109469
更新日期:2020-02-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.10.003
更新日期:2017-01-01 00:00:00
abstract::Wnt proteins are secreted glycoproteins that bind to the N-terminal extra-cellular cysteine-rich domain of the Frizzled (Fzd) receptor family. The Fzd receptors can respond to Wnt proteins in the presence of Wnt co-receptors to activate the canonical and non-canonical Wnt pathways. Recent studies indicated that, among...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2011.12.009
更新日期:2012-04-01 00:00:00
abstract::Transforming growth factory beta (TGF-beta) is a potent growth inhibitor of epithelial cells. One of the strategies used to elucidate the anti-proliferative mode of action of TGF-beta is to find out whether the receptor-generated signals interact with components of the basic machinery of the cell cycle. In this study ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(97)89890-7
更新日期:1997-05-01 00:00:00
abstract::The discovery of new signalling pathways is always followed by the development of pharmacological agents as drugs that can be used in the treatment of diseases resulting from a dysfunction of the signalling pathway in question. Apelin signalling plays a role in the central and peripheral regulation of the cardiovascul...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2004.09.018
更新日期:2005-04-01 00:00:00
abstract::Expression of the human alpha 2A-adrenergic receptor gene is induced by cAMP. The present studies were designed to define potential cAMP-responsive enhancer elements (CREs) in the promoter region of this gene. Regions from the 5'-flanking sequences of the gene were placed in a promoterless vector with a chloramphenico...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(94)90062-0
更新日期:1994-01-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.11.009
更新日期:2010-03-01 00:00:00
abstract::We have shown previously that the angiotensin II (Ang II) receptor AT2 reduces the intracellular levels of cGMP in Xenopus oocytes when activated by ligand binding, and the C-terminal cytoplasmic tail of the AT2 acts as a negative regulator of this function. Here we report the effects of mutations in the 2nd and 3rd i...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.08.007
更新日期:2005-03-01 00:00:00
abstract::Protein phosphatases play a key role in balancing the cellular responses to the transforming growth factor-β (TGFβ) signals. Several protein phosphatases have been attributed roles in the regulation of the TGFβ pathway. Among these, PPM1A is the only phosphatase reported to dephosphorylate SMAD2/3 in the nucleus. Howe...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.07.003
更新日期:2012-11-01 00:00:00
abstract::We have studied the effects of cholinergic agonists on the rates of insulin release and the concentrations of diacylglycerol (DAG) and intracellular free Ca2+ ([Ca2+]i) in the beta-cell line MIN6. Insulin secretion was stimulated by glucose, by glibenclamide and by bombesin. In the presence of glucose, both acetylchol...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(93)90038-n
更新日期:1993-11-01 00:00:00
abstract::Cell cycle progression from G2 phase into mitosis is regulated by a complex network of mechanisms, all of which finally control the timing of Cyclin B/CDK1 activation. PLK1 regulates a network of events that contribute to regulating G2/M phase progression. Here we have used a proteomics approach to identify proteins t...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.08.009
更新日期:2015-11-01 00:00:00
abstract::Calmodulin (CaM) antagonists, trifluoperazine (TFP) or calmidazolium (R24571), dose-dependently inhibited cAMP and folic acid (FA) chemotaxis in Dictyostelium. Developing, starved, and refed cells were compared to determine if certain CaM-binding proteins (CaMBPs) and CaM-dependent phosphorylation events could be iden...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00187-5
更新日期:2001-08-01 00:00:00
abstract::Extracellular signal regulated kinases (ERKs) are a class of MAP kinases that function in many signaling pathways in eukaryotic cells and in some cases, a single stimulus can activate more than one ERK suggesting functional redundancy or divergence from a common pathway. Dictyostelium discoideum encodes only two MAP k...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.01.008
更新日期:2010-05-01 00:00:00
abstract::In order to elucidate the molecular events in signal transduction, examination of the interaction between Ras and Raf-1 seems crucial. Many Raf-1 mutants have been investigated in terms of their binding activities to Ras, where only a few Ras mutants have been examined thus far. We have investigated the Raf-1-binding ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(96)00078-2
更新日期:1996-08-01 00:00:00
abstract::Desensitization of the micro-opioid receptor (MOR) has been implicated as an important regulatory process in the development of tolerance to opiates. Monitoring the release of intracellular Ca(2+) ([Ca(2+)](i)), we reported that [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO)-induced receptor desensitization req...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.12.003
更新日期:2010-04-01 00:00:00
abstract::CD44 is a hyaluronan binding cell surface signal transducing receptor that influences motility, cell survival and proliferation as well as the formation of tumor microenvironment. CD44 contains two variable regions encoded by variable exons. Alternative splicing, which is often deregulated in cancer, can produce vario...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2014.07.011
更新日期:2014-10-01 00:00:00