Abstract:
:Cbl-b, a mammalian homolog of Cbl, consists of an N-terminal region (Cbl-b-N) highly homologous to oncogenic v-Cbl, a Ring finger, and a C-terminal region containing multiple proline-rich stretches and potential tyrosine phosphorylation sites. In the present study, we demonstrate that upon engagement of the T cell receptor (TCR), endogenous Cbl-b becomes rapidly tyrosine-phosphorylated. In heterogeneous COS-1 cells, Cbl-b was phosphorylated on tyrosine residues by both Syk- (Syk/Zap-70) and Src- (Fyn/Lck) family kinases, with Syk kinase inducing the most prominent effect. Syk associates and phosphorylates Cbl-b in Jurkat T cells. A Tyr-316 Cbl-binding site in Syk was required for the association with and for the maximal tyrosine phosphorylation of Cbl-b. Mutation at a loss-of-function site (Gly-298) in Cbl-b-N disrupts its interaction with Syk. Cbl-b constitutively binds Grb2 and becomes associated with Crk-L upon TCR stimulation. The Grb2- and the Crk-L-binding regions were mapped to the C-terminus of Cbl-b. The Crk-L-binding sites were further determined to be Y655DVP and Y709KIP, with the latter being the primary binding site. Taken together, these results implicate that Cbl-b is involved in TCR-mediated intracellular signaling pathways.
journal_name
Oncogenejournal_title
Oncogeneauthors
Elly C,Witte S,Zhang Z,Rosnet O,Lipkowitz S,Altman A,Liu YCdoi
10.1038/sj.onc.1202411subject
Has Abstractpub_date
1999-02-04 00:00:00pages
1147-56issue
5eissn
0950-9232issn
1476-5594journal_volume
18pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Resistance to TGF-beta1 occurred in pancreatic cancer cells suggesting that inactivation of TGF-beta inhibitory signaling pathways may play an important role in human pancreatic cancer. The aim of our study was to determine the presence of alterations in the main putative components of the TGF-beta inhibitory signalin...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202118
更新日期:1998-10-15 00:00:00
abstract::Tumor suppressor p53 has been shown to repress expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a key mediator of tumor angiogenesis. The p63 gene, recently identified as a p53-relative, encodes multiple isoforms with structural and functional similarities and differenc...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205330
更新日期:2002-04-11 00:00:00
abstract::Expression of viral proteins may result in susceptibility of cells to the cytotoxic effect of Tumor Necrosis Factor Alpha (TNF). While murine C127 cells containing the bovine papillomavirus type 1 (BPV-1) genome were reported to exhibit increased TNF sensitivity, the gene(s) responsible was not identified. The BPV-1 E...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202373
更新日期:1999-01-21 00:00:00
abstract::We tested the cytotoxic action of 8-hydroxyguanine (8ohG) by observing the viability of several leukemic cell lines (KG-1, U937, Jurkat and K 562) in the presence of 8-hydroxydeoxyguanosine (8ohdG), a nucleoside of 8ohG. It was found that 8ohdG showed cytotoxic action only to KG-1 and that only KG-1 showed a homozygou...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203787
更新日期:2000-09-14 00:00:00
abstract::Loss of RASSF1A leads to several mitotic abnormalities, including cytokinesis failure and tetraploidization. Uncontrolled proliferation of tetraploid cells is known to trigger genomic instability and tumor development and is normally prevented through activation of a p53-dependent tetraploidy checkpoint. RASSF1A is th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.440
更新日期:2011-02-10 00:00:00
abstract::The role of TGF-β signaling in tumorigenesis is paradoxical: it can be tumor suppressive or tumor promotional, depending on context. The metastatic regulator, Six1, was recently shown to mediate this switch, providing a novel means to explain this elusive 'TGF-β paradox'. Herein, we identify a mechanism by which Six1 ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.11
更新日期:2012-12-13 00:00:00
abstract::The BRCA1-associated RING domain protein BARD1 acts with BRCA1 in double-strand break repair and ubiquitination. BARD1 plays a role as mediator of apoptosis by binding to and stabilizing p53, and BARD1-repressed cells are resistant to apoptosis. We therefore investigated the mechanism by which BARD1 induces p53 stabil...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208491
更新日期:2005-05-26 00:00:00
abstract::Tumor cells, stromal cell compartment and the extracellular matrix (ECM) together generate a multifaceted tumor microenvironment. Matrix metalloproteinases and their tissue inhibitors (TIMPs) provide a means for tumor-stromal interaction during tumorigenesis. Among TIMPs, TIMP-3 is uniquely localized to the ECM and is...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209104
更新日期:2006-01-26 00:00:00
abstract::Dysregulation of pleiotropic growth factors, receptors and their downstream signaling pathway components represent a central protumorigenic principle in human hepatocarcinogenesis. Especially the Insulin-like Growth Factor/IGF-1 receptor (IGF/IGF-1R), Hepatocyte Growth Factor (HGF/MET), Wingless (Wnt/beta-catenin/FZD)...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1209556
更新日期:2006-06-26 00:00:00
abstract::Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and loss of function assay...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0656-7
更新日期:2019-04-01 00:00:00
abstract::Tumor recurrence following treatment remains a major clinical challenge in oral cavity cancer. Cancer stem cells (CSCs) have been isolated from human oral cancers and been considered as the driving force of tumor recurrence and metastasis. However, it still remains unclear whether targeting CSCs in oral cancer is a cl...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0800-z
更新日期:2019-07-01 00:00:00
abstract::Replication origins are 'licensed' for a single initiation event by loading Mcm2-7 complexes during late mitosis and G1. Licensing is blocked at other cell cycle stages by the activity of cyclin-dependent kinases and a small protein called geminin. Here, we describe the effects of over-expressing a non-degradable form...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205910
更新日期:2002-09-26 00:00:00
abstract::We have used two different, but complementary assays to characterize functions of SV40 T antigen that are necessary for its ability to immortalize rat embryo fibroblasts. In accordance with previous work, we found that several functions were required. These include activities that map to the p53 binding domain and the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203154
更新日期:1999-12-02 00:00:00
abstract::RAS is a small GTP binding protein mutated in approximately 30% human cancer. Despite its important role in the initiation and progression of human cancer, the underlying mechanism of RAS-induced human epithelial transformation remains elusive. In this study, we probe the cellular and molecular mechanisms of RAS-media...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208753
更新日期:2005-09-08 00:00:00
abstract::YAP (Yes-associated protein) oncogene has been found to form a stable complex with members of the Angiomotin (Amot) family of proteins, which bind WW domains of YAP and sequester the protein in the cytoplasm and junctional complexes. The Amot-mediated retention of YAP in the cytoplasm results in the inhibition of its ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.216
更新日期:2012-01-05 00:00:00
abstract::We have previously reported that there is a high incidence of microsatellite instability (MSI) and germline mismatch repair gene mutation in colorectal cancer arising from young Hong Kong Chinese. Most of the germline mutations involve hMSH2, which is different from the mutation spectrum in the Western population. It ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204376
更新日期:2001-05-24 00:00:00
abstract::Making decisions between self-renewal and differentiation is a central ability of stem cells. Elucidation of molecular networks governing this decision is therefore of prime importance. A model of choice to explore this question is represented by chicken erythroid progenitors, in which self-renewal versus differentiat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207049
更新日期:2003-12-18 00:00:00
abstract::The effect of p53-dependent cell-cycle arrest and senescence on Emu-myc-induced B-cell lymphoma development remains controversial. To address this question, we crossed Emu-myc mice with the p53(515C) mutant mouse, encoding the mutant p53R172P protein that retains the ability to activate the cell-cycle inhibitor and se...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.423
更新日期:2010-03-04 00:00:00
abstract::Amplified segments of the long arm of chromosome 12 are frequently observed in human sarcomas. In most cases there are separate amplified regions around the MDM2 and CDK4 genes. Here we show recurrent amplification of a third region encompassing HMGIC, a human architectural transcription factor gene. Reduced amplifica...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201135
更新日期:1997-06-19 00:00:00
abstract::P21waf1/cip1 is a potent inhibitor of cell cycle progression and can inhibit the growth of both normal cells and cells transformed by a number of oncogenes. However, the ability of p21waf1/cip1 to inhibit the growth of cells that overexpress the transcriptional transactivator E2F1 is controversial: it has been reporte...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201849
更新日期:1998-06-18 00:00:00
abstract::The mechanisms by which the p53 tumour suppressor protein would, in vivo, co-ordinate the adaptive response to genotoxic stress is poorly understood. p53 has been shown to transactivate several genes that could be involved in two main cellular responses, growth arrest and apoptosis. To get further insight into the tis...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203366
更新日期:2000-02-03 00:00:00
abstract::von Hippel-Lindau (VHL) disease is a dominantly inherited family cancer syndrome characterized by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC) and phaeochromocytoma. Specific germline VHL mutations may predispose to haemangioblastomas, RCC and phaeochromocytoma t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209932
更新日期:2007-03-08 00:00:00
abstract::Acquired therapeutic resistance is the major drawback to effective systemic therapies for cancers. Aggressive triple-negative breast cancers (TNBC) develop resistance to chemotherapies rapidly, whereas the underlying mechanisms are not completely understood. Here we show that genotoxic treatments significantly increas...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.189
更新日期:2016-03-10 00:00:00
abstract::Cyclooxygenase-2 (COX-2) is involved in diverse processes such as inflammation, carcinogenesis and apoptosis. As COX-2 inhibitors interfere with these processes, inhibition of COX-2 has been suggested as a promising anticancer treatment. However, the role of COX-2 in modulation of apoptosis as well as the death pathwa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206837
更新日期:2003-09-11 00:00:00
abstract::Atypical protein kinase C (aPKC) and Lethal giant larvae (Lgl) regulate apical-basal polarity in Drosophila and mammalian epithelia. At the apical domain, aPKC phosphorylates and displaces Lgl that, in turn, maintains aPKC inactive at the basolateral region. The mutual exclusion of these two proteins seems to be cruci...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210389
更新日期:2007-08-30 00:00:00
abstract::To dissect the p53-dependent apoptotic pathway, events following induction of temperature sensitive (ts) p53val138 were studied in a Ewing tumor cell line. Transcriptional deregulation of p53 targets first observable after 1 h at 32 degrees C preceded activation of caspases and the break-down of mitochondrial respirat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203780
更新日期:2000-08-24 00:00:00
abstract::Bladder cancer is one of the most common causes of death in industrialized countries. New tumor markers and therapeutic approaches are still needed to improve the management of bladder cancer patients. Choline kinase-alpha (ChoKalpha) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.91
更新日期:2009-07-02 00:00:00
abstract::A seven-transmembrane protein, frizzled, has been implicated in a planar cell polarity (PCP) pathway as well as the canonical Wnt signaling pathway. Although both pathways require a cytoplasmic protein, dishevelled, the molecular mechanism by which frizzled regulates intracellular signaling remains to be elucidated. I...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207817
更新日期:2004-08-12 00:00:00
abstract::The ability of glioma cells to migrate great distances from a primary tumor mass is the primary cause of tumor recurrence. The urokinase-type plasminogen activator (uPA) is a serine protease that can initiate proteolytic cascades, which result in remodeling of extracellular matrix and basement membrane, allowing cells...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206164
更新日期:2003-01-23 00:00:00
abstract::The RAF-mitogen-activated protein kinase kinase 1/2-extracellular signal-regulated kinase 1/2 (RAF-MEK1/2-ERK1/2) pathway is activated in many human tumours and can protect cells against growth factor deprivation; however, most such studies have relied upon overexpression of RAF or MEK constructs that are not found in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.335
更新日期:2008-12-04 00:00:00