Abstract:
:Normal signaling by TGFbeta, in the absence of serum or exogenous factors, involves a rapid activation of Ras, Erks, and Sapks in proliferating cultures of TGFbeta-sensitive untransformed epithelial cells and human carcinoma cells. Expression of either RasN17 or dominant-negative (DN) MKK4, or addition of the MEK1 inhibitor PD98059, can block the ability of TGFbeta to induce AP-1 complex formation at the TGFbeta(1) promoter and to autoinduce its own production. The primary components present in this TGFbeta-stimulated AP-1 complex are JunD and Fra-2, although c-Jun, and possibly Fos B, may also be present. While there are two potential Smad binding elements (SBE's) in the TGFbeta(1) promoter, supershift assays suggest that at least one of these does not bind Smad4, and the other is unable to bind factors activated by TGFbeta. In contrast, TGFbeta autoinduction is Smad3-dependent, as DN Smad3 inhibits the ability of TGFbeta to stimulate TGFbeta(1) promoter activity. Our results indicate that TGFbeta can activate both the MKK4/Sapk and MEK/Erk pathways, through Ras and TGFbeta R(I) and R(II), to induce TGFbeta(1) production; Smad4 does not appear to be involved, and Smad3 appears to function independently of this Smad4. We also demonstrate that activation of the Ras/Mapk pathway by TGFbeta positively modulates Smad1-signaling-pathway activation by TGFbeta. In addition, Smad1 could enhance TGFbeta activation of the SBE reporter SBE-luc and this effect could be blocked by co-expression of a DN TGFbeta R(I) receptor or by the MEK1 inhibitor PD98059. This cross-talk between the MEK/Erk and Smad1 pathways was mediated through the four Erk consensus phosphorylation sites in the linker region of Smad1. Mutation of these sites resulted in a loss of the ligand-dependence of both Smad1-Smad4 interactions and nuclear accumulation of Smad1, as well as a loss of the ability of Smad1 to enhance TGFbeta-mediated SBE activation. Our results provide evidence that Erk-mediated phosphorylation of Smad1 in response to TGFbeta is critical for regulating Smad1 subcellular localization; this may be a key determinant in maintaining TGFbeta-dependent transcriptional activation.
journal_name
Cytokine Growth Factor Revjournal_title
Cytokine & growth factor reviewsauthors
Mulder KMdoi
10.1016/s1359-6101(99)00026-xsubject
Has Abstractpub_date
2000-03-01 00:00:00pages
23-35issue
1-2eissn
1359-6101issn
1879-0305pii
S1359-6101(99)00026-Xjournal_volume
11pub_type
杂志文章,评审abstract::Interactions between tumor cells and their microenvironment have been shown to play a very significant role in the initiation, progression, and invasiveness of cancer. These tumor-stromal interactions are capable of altering the delivery and effectiveness of therapeutics into the tumor and are also known to influence ...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2010.02.014
更新日期:2010-04-01 00:00:00
abstract::The BMP signaling pathway controls a number of cell processes during development and in adult tissues. At the cellular level, ligands of the BMP family act by binding a hetero-tetrameric signaling complex, composed of two type I and two type II receptors. BMP ligands make use of a limited number of receptors, which in...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2009.10.008
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abstract::The wider use of allogeneic stem cell transplantation (allo-SCT) is still limited by the immunologic recognition and destruction of host tissues, termed graft-versus-host disease (GVHD). The role of inflammatory cytokines such as TNF-alpha and IL-1, and their impact on immune effectors (mainly CD4+ and CD8+ T) cells h...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2007.10.010
更新日期:2008-02-01 00:00:00
abstract::A number of cell surface growth factor receptors are subject to presenilin-dependent regulated intramembrane proteolysis (PS-RIP) after ligand binding and/or ectodomain cleavage. PS-RIP is mediated by a highly conserved multi-component membrane-bound protease, termed gamma-secretase, responsible for generating Alzheim...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2004.04.001
更新日期:2004-10-01 00:00:00
abstract::The exposure of cells to TGF-beta1 can trigger a variety of cellular responses including the inhibition of cell growth, migration, differentiation and apoptosis. TGF-beta1-regulated apoptosis is cell type and context-dependent, indeed TGF-beta1 provides signals for both cell survival or apoptosis. The molecular mechan...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2004.11.002
更新日期:2005-02-01 00:00:00
abstract::The recent discovery of thrombopoietin has enhanced our understanding of both hematopoiesis and platelet production. Thrombopoietin supports hematopoietic stem cell survival and expansion as well as promoting all aspects of megakaryocyte development. The hormone displays many structural similarities to other members o...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/s1359-6101(01)00030-2
更新日期:2002-02-01 00:00:00
abstract::Fibrosis leads to destruction of organ architecture accompanied by chronic inflammation and loss of function. Fibrosis affects nearly every organ in the body and accounts for ∼45% of total deaths worldwide. Over the past decade, tremendous progress has been made in understanding the basic mechanisms leading to organ f...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2020.08.004
更新日期:2020-08-30 00:00:00
abstract::Serine/Arginine splicing factor 1 (SRSF1) is an RNA binding protein abundantly expressed in most tissues. The pleiotropic functions of SRSF1 exert multiple roles in gene expression by regulating major steps in transcription, processing, export through the nuclear pores and translation of nascent RNA transcripts. The a...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2020.10.008
更新日期:2020-11-02 00:00:00
abstract::S100A7 (psoriasin), an EF-hand type calcium binding protein localized in epithelial cells, regulates cell proliferation and differentiation. An S100A7 overexpression may occur in response to inflammatory stimuli, such in psoriasis, a chronic inflammatory autoimmune-mediated skin disease. Increasing evidence suggests t...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2016.01.002
更新日期:2016-12-01 00:00:00
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journal_title:Cytokine & growth factor reviews
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.cytogfr.2011.07.001
更新日期:2011-08-01 00:00:00
abstract::Osteoarthritis (OA) is the most common form of arthritic disease, leading to disability and impaired quality of life and no curative treatments exist. Increasing evidence indicates that low-grade inflammation plays a pivotal role in the onset and progression of OA. In this review, we summarize emerging findings on the...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2019.03.004
更新日期:2019-04-01 00:00:00
abstract::Tuberculosis is a global health calamity. The causative agent, Mycobacterium tuberculosis (M. tuberculosis), has evolved elaborate survival mechanisms in humans, allowing it to remain in a clinically latent infection state, constantly engaging the immune system, with the possibility to progress to active disease. Auto...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2013.01.002
更新日期:2013-08-01 00:00:00
abstract::Chemotherapy remains a common mode of anticancer treatment even though in most cancer indications the therapeutic approach is not effective and ultimately associated with the onset of chemoresistance. A better understanding of genetic differences in tumors ushered in the era of targeted therapy which has revolutionize...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2010.02.001
更新日期:2010-04-01 00:00:00
abstract::Heparin-binding EGF-like growth factor (HB-EGF), which belongs to the EGF-family growth factors, is synthesized as a membrane-anchored form (proHB-EGF). Proteolytic cleavage of proHB-EGF at the extracellular domain yields the soluble form of HB-EGF (sHB-EGF). ProHB-EGF is not only the precursor molecule for sHB-EGF bu...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/s1359-6101(00)00013-7
更新日期:2000-12-01 00:00:00
abstract::TGF-beta signaling regulates tumorigenesis and in human cancer its signaling pathways are often modified during tumor progression. Prior to initiation and early during progression TGF-beta acts upon the epithelium as a tumor suppressor, however at later stages it is often a tumor promoter. Over the years, many studies...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2005.09.006
更新日期:2006-02-01 00:00:00
abstract::Apo2 ligand or tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL) is one of several members of the TNF gene superfamily that induce apoptosis through engagement of death receptors. Apo2L/TRAIL is unusual as compared to any other cytokine as it interacts with a complex system of receptors: two ...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/s1359-6101(03)00029-7
更新日期:2003-06-01 00:00:00
abstract::MicroRNAs are involved in multiple pathophysiological networks and in the pathogenesis of a broad spectrum of human disorders, including cancer and inflammatory diseases. Impaired linear growth is encountered in children with chronic inflammatory conditions such as cystic fibrosis, inflammatory bowel diseases, juvenil...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2017.12.004
更新日期:2018-02-01 00:00:00
abstract::The WFIKKN (WAP, Follistatin/kazal, Immunoglobulin, Kunitz and Netrin domain-containing) protein family is composed of two multidomain proteins: WFIKKN1 and WFIKKN2. They were formed by domain shuffling and are likely present in deuterostoms. The WFIKKN (also called GASP) proteins are well known for their function in ...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2016.06.003
更新日期:2016-12-01 00:00:00
abstract::Prostate cancer (PCa), the most common non-skin cancer in men, is a worldwide health concern. Treatment options for aggressive PCa are limited to androgen deprivation therapies (ADT), which are ineffective, with robust diagnostic options also being limited. The prostate specific antigen (PSA) test, for instance, is su...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2012.04.004
更新日期:2012-06-01 00:00:00
abstract::Activins are transforming growth factor beta superfamily members, which were originally identified as inducers of follicle-stimulating hormone release from the pituitary. In recent years, however, additional functions of activins have been discovered, including a role in the morphogenesis of various tissues and organs...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2006.01.001
更新日期:2006-06-01 00:00:00
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journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2013.03.005
更新日期:2013-06-01 00:00:00
abstract::The coronavirus disease 19 (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) had turned out to be highly pathogenic and transmittable. Researchers throughout the globe are still struggling to understand this strain's aggressiveness in search of putative therapies for its contro...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2020.08.002
更新日期:2020-08-25 00:00:00
abstract::Viral infection is detected by cellular sensors as foreign nucleic acid and initiates innate antiviral responses, including the activation of type I interferon (IFN) and proinflammatory cytokines. Recent advances in cytoplasmic virus sensors highlight their essential role in the induction of innate immunity. Moreover,...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2007.06.023
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abstract::Interferon-beta (IFN-beta) is routinely prescribed as an immunomodulatory treatment for multiple sclerosis (MS), but is associated with variable clinical efficacy. Ideally an early predictor of response status would allow more rational provision of this therapy. Both pharmacogenomic and expression analysis have highli...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2007.04.012
更新日期:2007-06-01 00:00:00
abstract::Recent achievements in the biology and the function of adipose tissue have regarded white adipose tissue (WAT) as an important endocrine and secretory organ. Releasing a series of multiple-function mediators, WAT is involved in a wide spectrum of diseases, including not only cardiovascular and metabolic complications,...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2012.07.004
更新日期:2013-02-01 00:00:00
abstract::Angiopoietin-1 and -2 are endogenous ligands for the vascular endothelial receptor tyrosine kinase Tie2. Signalling by angiopoietin-1 promotes vascular endothelial cell survival and the sprouting and reorganisation of blood vessels, as well as inhibiting activation of the vascular endothelial barrier to reduce leakage...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2013.05.009
更新日期:2013-12-01 00:00:00
abstract::The clinical exploitation of type I interferon (IFN) as an antiviral and antineoplastic agent is based on the properties originally attributed to this cytokine family, with schedules reflecting only their antiviral and antiproliferative activities. Nevertheless, type I IFN has emerged as a central activator of the inn...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2014.12.006
更新日期:2015-04-01 00:00:00
abstract::The cyclins are a family of proteins that are centrally involved in cell cycle regulation and which are structurally identified by conserved "cyclin box" regions. They are regulatory subunits of holoenzyme cyclin-dependent kinase (CDK) complexes controlling progression through cell cycle checkpoints by phosphorylating...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/s1359-6101(00)00018-6
更新日期:2001-03-01 00:00:00
abstract::Sphingosine 1-phosphate (S1P)-metabolizing enzymes regulate the level of bioactive sphingolipids that have curative potential. Recently, S1P-metabolizing enzymes such as sphingosine kinase 1 and S1P lyase were shown to regulate influenza virus replication and the virus-induced cytopathogenicity. The mechanism appeared...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2010.12.001
更新日期:2011-02-01 00:00:00
abstract::Tumors have developed different strategies to escape immune recognition. This could be due to altered expression of classical and non-classical human leukocyte antigens (HLA), co-inhibitory or co-stimulatory molecules as well as components of the interferon signaling pathway. Furthermore, changes in the tumor microenv...
journal_title:Cytokine & growth factor reviews
pub_type: 杂志文章,评审
doi:10.1016/j.cytogfr.2017.07.001
更新日期:2017-08-01 00:00:00