Abstract:
:The interleukin-2 (IL-2) receptor (IL-2R) consists of three distinct subunits (alpha, beta, and gamma c) and regulates proliferation of T lymphocytes. Intracellular signalling results from ligand-mediated heterodimerization of the cytoplasmic domains of the beta and gamma c chains. To identify the residues of gamma c critical to this process, mutations were introduced into the cytoplasmic domain, and the effects on signalling were analyzed in the IL-2-dependent T-cell line CTLL2 and T-helper clone D10, using chimeric IL-2R chains that bind and are activated by granulocyte-macrophage colony-stimulating factor. Whereas previous studies of fibroblasts and transformed T cells have suggested that signalling by gamma c requires both membrane-proximal and C-terminal subdomains, our results for IL-2-dependent T cells demonstrate that the membrane-proximal 52 amino acids are sufficient to mediate a normal proliferative response, including induction of the proto-oncogenes c-myc and c-fos. Although gamma c is phosphorylated on tyrosine upon receptor activation and could potentially interact with downstream molecules containing SH2 domains, cytoplasmic tyrosine residues were dispensable for mitogenic signalling. However, deletion of a membrane-proximal region conserved among other cytokine receptors (cytoplasmic residues 5 to 37) or an adjacent region unique to gamma c (residues 40 to 52) abrogated functional interaction of the receptor chain with the tyrosine kinase Jak3. This correlated with a loss of all signalling events analyzed, including phosphorylation of the IL-2R beta-associated kinase Jak1, expression of c-myc and c-fos, and induction of the proliferative response. Thus, it appears in T cells that Jak3 is a critical mediator of mitogenic signaling by the gamma c chain.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Nelson BH,Lord JD,Greenberg PDdoi
10.1128/mcb.16.1.309subject
Has Abstractpub_date
1996-01-01 00:00:00pages
309-17issue
1eissn
0270-7306issn
1098-5549journal_volume
16pub_type
杂志文章abstract::The C-terminal domain of the RNA polymerase II largest subunit (the Rpb1 CTD) is composed of tandem heptad repeats of the consensus sequence Y(1)S(2)P(3)T(4)S(5)P(6)S(7). We reported previously that Thr 4 is phosphorylated and functions in histone mRNA 3'-end formation in chicken DT40 cells. Here, we have extended our...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00181-14
更新日期:2014-07-01 00:00:00
abstract::The ability of basic helix-loop-helix muscle regulatory factors (MRFs), such as MyoD, to convert nonmuscle cells to a myogenic lineage is regulated by numerous growth factor and oncoprotein signaling pathways. Previous studies have shown that H-Ras 12V inhibits differentiation to a skeletal muscle lineage by disruptin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.7.3547
更新日期:1997-07-01 00:00:00
abstract::Rad53 of Saccharomyces cerevisiae is a checkpoint kinase whose structure and function are conserved among eukaryotes. When a cell detects damaged DNA, Rad53 activity is dramatically increased, which ultimately leads to changes in DNA replication, repair, and cell division. Despite its central role in checkpoint signal...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.10.3405-3416.2003
更新日期:2003-05-01 00:00:00
abstract::Normal cells do not divide indefinitely due to a process known as replicative senescence. Human cells arrest growth with a senescent phenotype when they acquire one or more critically short telomeres as a consequence of cell division. Recent evidence suggests that certain types of DNA damage, chromatin remodeling, and...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.1.273-285.2000
更新日期:2000-01-01 00:00:00
abstract::Telomere maintenance is required for chromosome stability, and telomeres are typically replicated by the action of the reverse transcriptase telomerase. In both tumor and yeast cells that lack telomerase, telomeres are maintained by an alternative recombination mechanism. Genetic studies have led to the identification...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.16.5679-5687.2002
更新日期:2002-08-01 00:00:00
abstract::Unlike the DNA of higher eucaryotes, the DNA of Saccharomyces cerevisiae (bakers' yeast) is not methylated. Introduction of the Escherichia coli dam gene into yeast cells results in methylation of the N-6 position of adenine. The UV excision repair system of yeast cells specifically responds to the methylation, sugges...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.10.3555
更新日期:1986-10-01 00:00:00
abstract::We have constructed a recombinant pBR322 plasmid composed of a subgenomic transforming fragment of bovine papillomavirus DNA and the hepatitis B surface antigen gene from cloned hepatitis B virus DNA and used it for transfection of NIH 3T3 mouse fibroblasts. The transformed cells retain the plasmids in extrachromosoma...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.6.1032
更新日期:1983-06-01 00:00:00
abstract::Vanin-1 is an epithelial ectoenzyme with pantetheinase activity and generating the amino-thiol cysteamine through the metabolism of pantothenic acid (vitamin B(5)). Here we show that Vanin-1(-/-) mice, which lack cysteamine in tissues, exhibit resistance to oxidative injury induced by whole-body gamma-irradiation or p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.16.7214-7224.2004
更新日期:2004-08-01 00:00:00
abstract::Pax transactivation domain-interacting protein (PTIP, or PAXIP1) is required for mouse development and has been implicated in DNA damage responses and histone modification. However, the physiological roles of PTIP during embryogenesis remain unclear due to early embryonic lethality of null mutants. We describe two N-e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00727-08
更新日期:2008-10-01 00:00:00
abstract::The androgen receptor (AR) is a nuclear hormone receptor superfamily member that conveys both trans repression and ligand-dependent trans-activation function. Activation of the AR by dihydrotestosterone (DHT) regulates diverse physiological functions including secondary sexual differentiation in the male and the induc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.10.3373-3388.2002
更新日期:2002-05-01 00:00:00
abstract::E3 ubiquitin ligases, which target specific molecules for proteolytic destruction, have emerged as key regulators of immune functions. Several E3 ubiquitin ligases, including c-Cbl, Cbl-b, GRAIL, Itch, and Nedd4, have been shown to negatively regulate T-cell activation. Here, we report that the HECT-type E3 ligase AIP...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00407-09
更新日期:2009-10-01 00:00:00
abstract::The niaD and niiA genes of Aspergillus nidulans, which code, respectively, for nitrate and nitrite reductases, are divergently transcribed, and their ATGs are separated by 1,200 bp. The genes are under the control of the positively acting NirA transcription factor, which mediates nitrate induction. The DNA binding dom...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.10.5688
更新日期:1995-10-01 00:00:00
abstract::Malignant melanoma, an aggressive and increasingly common cancer, is characterized by a strikingly high rate (70%) of mutations in BRAF, a key component of the mitogen-activated protein (MAP) kinase signaling pathway. How signaling events downstream from BRAF affect the underlying program of gene expression is poorly ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.7.2923-2931.2004
更新日期:2004-04-01 00:00:00
abstract::Protein ubiquitination plays a key role in the regulation of a variety of DNA repair mechanisms. Protein ubiquitination is controlled by the coordinate activity of ubiquitin ligases and deubiquitinating enzymes (DUBs). The deubiquitinating enzyme USP1 regulates DNA repair and the Fanconi anemia pathway through its ass...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05058-11
更新日期:2011-06-01 00:00:00
abstract::X-linked inhibitor of apoptosis (XIAP) is an inhibitor of apoptotic cell death that protects cells by caspase-dependent and independent mechanisms. In a screen for molecules that participate with XIAP in regulating cellular activities, we identified apoptosis-inducing factor (AIF) as an XIAP binding protein. Baculovir...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01065-07
更新日期:2008-01-01 00:00:00
abstract::Krüppel-like factors 3 and 8 (KLF3 and KLF8) are highly related transcriptional regulators that bind to similar sequences of DNA. We have previously shown that in erythroid cells there is a regulatory hierarchy within the KLF family, whereby KLF1 drives the expression of both the Klf3 and Klf8 genes and KLF3 in turn r...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00074-13
更新日期:2013-08-01 00:00:00
abstract::The mechanism by which the maize autonomous Ac transposable element gives rise to nonautonomous Ds elements is largely unknown. Sequence analysis of native maize Ds elements indicates a complex chimeric structure formed through deletions of Ac sequences with or without insertions of Ac-unrelated sequence blocks. These...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.11.6294
更新日期:1997-11-01 00:00:00
abstract::The proto-oncogene c-myb is essential for a controlled balance between cell growth and differentiation. Aberrant c-Myb activity has been reported for numerous human cancers, and enforced c-Myb transcription can transform cells of lymphoid origin by stimulating cellular proliferation and inhibiting apoptotic pathways. ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.21.7391-7402.2001
更新日期:2001-11-01 00:00:00
abstract::ICP4 of herpes simplex virus is responsible for the activation of viral transcription during infection. It also efficiently activates and represses transcription in vitro depending on the promoter context. The contacts made between ICP4 and the cellular proteins that result in activated transcription have not been ide...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.6.3085
更新日期:1996-06-01 00:00:00
abstract::Endonuclease G (endo G) is one of the most abundant nucleases in eukaryotic cells. It is encoded in the nucleus and imported to the mitochondrial intermembrane space. This nuclease is active on single- and double-stranded DNA. We genetically disrupted the endo G gene in mice without disturbing a conserved, overlapping...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.1.294-302.2005
更新日期:2005-01-01 00:00:00
abstract::The recruitment of corepressors by DNA-bound repressors is likely to be a critical rate-limiting step in the transcriptional regulation of many genes. An excellent paradigm for such an interaction is the association of the basic helix-loop-helix zipper protein Mad1 with the corepressor mSin3A. When bound together, the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.7.2698-2709.2004
更新日期:2004-04-01 00:00:00
abstract::The neutral/neutral two-dimensional (2-D) gel replicon mapping technique has been used to great advantage to localize and characterize origins of replication. Interestingly, many yeast origins display a composite pattern consisting of both a bubble arc and a single-fork arc. Moreover, in every instance in which neutra...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.9.4915
更新日期:1996-09-01 00:00:00
abstract::The homeobox gene HOXA9 has recently been shown to be an important regulator of endothelial cell (EC) differentiation and activation in addition to its role in embryonic development and hematopoiesis. In this report, we have determined that the EC-leukocyte adhesion molecule E-selectin is a key target for HOXA9. The d...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00052-07
更新日期:2007-06-01 00:00:00
abstract::We analyzed the impact of a GAGA element on a transgenic promoter in Drosophila melanogaster that was activated by proteins composed of the Tet(on) DNA binding domain and either the heat shock factor (HSF) activation domain or a potent subdomain of VP16. Permanganate footprinting was used to monitor polymerase II (Pol...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.9.3543-3552.2005
更新日期:2005-05-01 00:00:00
abstract::The signal-transducing adaptor protein 2 (STAP-2) is a recently identified adaptor protein that contains a pleckstrin homology (PH) and Src homology 2 (SH2)-like domains, as well as a proline-rich domain in its C-terminal region. In previous studies, we demonstrated that STAP-2 binds to MyD88 and IKK-alpha or IKK-beta...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00194-08
更新日期:2008-08-01 00:00:00
abstract::An in silico screen for myogenic long noncoding RNAs (lncRNAs) revealed nine lncRNAs that are upregulated more than 10-fold in myotubes versus levels in myoblasts. One of these lncRNAs, MyoD upstream noncoding (MUNC, also known as DRR(eRNA)), is encoded 5 kb upstream of the transcription start site of MyoD, a myogenic...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01079-14
更新日期:2015-02-01 00:00:00
abstract::Phosphorylation is believed to be one of the mechanisms by which p53 becomes activated or stabilized in response to cellular stress. Previously, p53 was shown to interact with three components of transcription factor IIH (TFIIH): excision repair cross-complementing types 2 and 3 (ERCC2 and ERCC3) and p62. This communi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.10.5923
更新日期:1997-10-01 00:00:00
abstract::Mouse mammary epithelial cells can be transformed in primary cultures to preneoplastic and neoplastic states when treated with N-methyl-N-nitrosourea (MNU). Mammary carcinomas arising from MNU-induced hyperplastic alveolar nodules (a type of mouse mammary preneoplastic lesion) contained transforming c-Ki-ras genes whe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.4.1593
更新日期:1990-04-01 00:00:00
abstract::Malignant gliomas are highly lethal neoplasms with limited treatment options. We previously found that the heparan sulfate proteoglycan glypican 1 (GPC1) is universally and highly expressed in human gliomas. In this study, we investigated the biological activity of GPC1 expression in both human glioma cells and normal...
journal_title:Molecular and cellular biology
pub_type: 杂志文章,收录出版
doi:10.1128/MCB.00238-13
更新日期:2013-11-01 00:00:00
abstract::A region of the Saccharomyces cerevisiae mitochondrial cytochrome b gene encompassing the entire terminal intron plus flanking exonic sequences has been cloned in an SP6 vector. A runoff transcript prepared from this construct as well as the native cytochrome b pre-mRNA containing the terminal intervening sequence wer...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.7.2545
更新日期:1987-07-01 00:00:00