Abstract:
:Grb2 is an adaptor protein that links receptor and cytoplasmic tyrosine kinases to the Ras signalling pathway by binding the Ras-specific guanine nucleotide exchange factor, Sos1, through its SH3 domains. The Grb2-SH3 domain binding has been localized to the carboxy-terminal two hundred amino acids of Sos1 (Sos1-c). By using real time biospecific interaction analysis (BIAcore), we studied the kinetic parameters and binding affinity of the Grb2-Sos1-c interaction. The binding of Grb2 to Sos1-c is a high affinity interaction with a moderate association rate (9.45 x 10(4) per M per s), a slow dissociation rate (13.8 x 10(-5) s), and an affinity constant of 1.48 nM. BIAcore measurements on isolated N-terminal and C-terminal SH3 domains (NSH3 and CSH3) further indicate that the high affinity Grb2-Sos1-c interaction is primarily mediated through the NSH3 domain (Kd = 1.68 nM). The CSH3 domain shows substantially reduced binding to Sos1-c in these measurements. Inhibition studies with BIAcore using proline rich peptides derived from the C-terminus of Sos1 show that there is a single major binding site for Grb2 in Sos1. This binding site is contained within the peptide N20, which corresponds to amino acids 1143-1162 of Sos1. This peptide completely blocks the Grb2-Sos1-c and NSH3-Sos1-c interactions with IC50 values of 8 microM and 4 microM respectively. The discrete interaction between the NSH3 domain and the N20 peptide may be amenable for drug discovery through screening or peptidomimetic approaches.
journal_name
Oncogenejournal_title
Oncogeneauthors
Sastry L,Lin W,Wong WT,Di Fiore PP,Scoppa CA,King CRsubject
Has Abstractpub_date
1995-09-21 00:00:00pages
1107-12issue
6eissn
0950-9232issn
1476-5594journal_volume
11pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::The genetically heterogeneous triple-negative breast cancer (TNBC) continues to be an intractable disease, due to lack of effective targeted therapies. Gene amplification is a major event in tumorigenesis. Genes with amplification-dependent expression are being explored as therapeutic targets for cancer treatment. In ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1279-3
更新日期:2020-05-01 00:00:00
abstract::B-cell CLL/lymphoma 6 (BCL6) exerts oncogenic effects in several human hematopoietic malignancies including chronic myeloid leukemia (CML), where BCL6 expression was shown to be essential for CML stem cell survival and self-renewal during imatinib mesylate (IM) treatment. As several lines of evidence suggest that inte...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.85
更新日期:2017-08-10 00:00:00
abstract::Snail1 is a master regulator of the epithelial-mesenchymal transition (EMT) and has been implicated in key tumor biological processes such as invasion and metastasis. It has been previously shown that poly(ADP-ribose) polymerase-1 (PARP-1) knockdown, but not PARP inhibition, downregulates the expression of Snail1. In ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.153
更新日期:2011-10-20 00:00:00
abstract::Radicicol, a macrocyclic anti-fungal antibiotic, has the ability to suppress transformation by diverse oncogenes such as Src, Ras and Mos. Despite this useful property, the mechanism by which radicicol exerts its anti-transformation effects is currently unknown. To understand the transformation-suppressing effects of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201790
更新日期:1998-05-01 00:00:00
abstract::The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple developmental defects and cancer susceptibility, in particular to basal cell carcinomas (BCCs). Medulloblastomas, primitive neuroectodermal tumours (PNETs) arising in childhood, occur in about 3-5% of NBCCS pa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201340
更新日期:1997-07-17 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::Advanced Bladder Cancer (BLCA) remains a clinical challenge that lacks effective therapeutic measures. Here, we show that distinct, stage-wise metabolic alterations in BLCA are associated with the loss of function of aldehyde oxidase (AOX1). AOX1 associated metabolites have a high predictive value for advanced BLCA an...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0902-7
更新日期:2020-10-01 00:00:00
abstract::An adenovirus mutant lacking the expression of the large E1B protein (DeltaE1B) has been reported to replicate selectively in cells lacking the expression of functionally wild-type (wt) p53. Based on these results the DeltaE1B or ONYX-015 virus has been proposed to be an oncolytic virus which might be useful to treat ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202886
更新日期:1999-09-09 00:00:00
abstract::14-3-3sigma proteins regulate numerous cellular processes that are important to cancer development. One of its biological roles involves G2 cell-cycle arrest following DNA damage. It has also been reported that the loss of 14-3-3sigma expression via CpG methylation may contribute to malignant transformation by impairi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209462
更新日期:2006-08-03 00:00:00
abstract::Mouse embryonic stem (ES) cells are known to express D-type cyclins at very low levels and these levels increase dramatically during in vitro and in vivo differentiation. Here, we investigate some of the signalling pathways regulating expression of cyclin D1 and progression to S phase, the Ras/Extracellular signal-reg...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205728
更新日期:2002-08-15 00:00:00
abstract::Interleukin-6 (IL-6) inhibits the growth of melanocytes and of early stage melanoma cells, but not that of advanced melanoma cells. The in vitro IL-6 response can be restored in the highly metastatic melanoma B16-F10.9 by addition of recombinant soluble IL-6 receptor alpha-chain (sIL-6R). The F10.9 cells then undergo ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201213
更新日期:1997-07-31 00:00:00
abstract::SIAH-1 and SIAH-2 are the human members of an evolutionary highly conserved E3 ligase family. SIAH-1 is a p53 and p21(Waf-1/Cip-1) induced gene during apoptosis and tumor suppression. In stable-transfected clones of MCF-7 cells, SIAH-1 overexpression was associated with apoptosis, mitotic alterations and p21(Waf-1/Cip...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206994
更新日期:2003-12-04 00:00:00
abstract::We have previously demonstrated that the expression of FGFR3 is frequently downregulated in colorectal carcinoma cells. Here we have shown that FGFR1 is overexpressed in colorectal carcinoma cells and the gene expressions between FGFR1 and FGFR3 are mutually exclusive. Moreover, we have also shown that the disruption ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208254
更新日期:2005-01-27 00:00:00
abstract::Proliferating cell nuclear antigen (PCNA) has no intrinsic enzymatic function, but functions as a sliding platform to mediate protein interactions with the DNA strand. Many proteins interact with PCNA through a small conserved motif with consensus QxxLxxFF. This work uses Schizosaccharomyces pombe and human cells to a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209320
更新日期:2006-05-11 00:00:00
abstract::Nuclear activated β-catenin plays a causative role in colorectal cancers (CRC) but remains an elusive therapeutic target. Using human CRC cells harboring different Wnt/β-catenin pathway mutations in APC/KRAS or β-catenin/KRAS genes, and both genetic and pharmacological knockdown approaches, we show that oncogenic β-ca...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0170-y
更新日期:2018-06-01 00:00:00
abstract::As part of a cloning strategy to identify genes involved in early mouse liver development we have isolated Praja1, a gene with similar sequences to the Drosophila melanogaster gene goliath (gl) which is involved in the fate of mesodermal cells ultimately forming gut musculatures, fat body, and the heart. Praja1 is a 2...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201405
更新日期:1997-11-06 00:00:00
abstract::Ubiquitin-dependent mechanisms have emerged as essential regulatory elements controlling cellular levels of Smads and TGFβ-dependent biological outputs such as epithelial-mesenchymal transition (EMT). In this study, we identify a HECT E3 ubiquitin ligase known as WWP2 (Full-length WWP2-FL), together with two WWP2 isof...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.617
更新日期:2011-05-26 00:00:00
abstract::Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are an enzyme family that plays a key role in cell proliferation control by dephosphorylating/inactivating both tyrosine kinase receptors (such as PDGF, insulin, and ephrin receptors) and docking proteins (such, as beta-catenin) endowed with both adhesion a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207508
更新日期:2004-05-13 00:00:00
abstract::Although apoptosis can be induced by the enforced expression of exogenously introduced c-myc genes, it is not clear whether overexpression resulting from the amplification of the resident c-myc gene in tumor cells is sufficient to induce apoptosis. We have investigated the relationship between c-myc gene amplification...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202309
更新日期:1999-01-14 00:00:00
abstract::The human ret proto-oncogene (proto-ret), encoding a receptor tyrosine kinase, is highly expressed in neuroblastomas, medullary thyroid carcinomas (MTCs) and pheochromocytomas, which are all tumors of cells originating from the neural crest. In studies on the transcription mechanism of proto-ret, we identified the tra...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::The PLZF gene was identified first by its fusion with the retinoic acid receptor alpha gene in the t(11;17) translocation associated with a retinoic acid resistant form of acute promyelocytic leukemia (APL). It encodes a krüppel-like zinc finger protein with a POZ domain shared with a subset of regulatory proteins inc...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202043
更新日期:1998-05-14 00:00:00
abstract::Cytokine receptors have different signaling requirements which ultimately lead to various physiological responses. In an effort to precisely characterize the molecular determinants involved in the proliferative response mediated by cytokines, we examine dose-dependent proliferation of the betac (GM-CSF, IL-3, IL-5) an...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205444
更新日期:2002-05-16 00:00:00
abstract::The VN-11 recombinant retroviruses, originally generated by co-transfection of the avian MH2 and AKRv viral genomes, were molecularly cloned from an infected mouse cell line named N11. The analysis of the proviral genome sequence from one of these recombinants showed a possible envAKR-mycMH2 fusion. Point mutations we...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::To gain a more complete understanding of c-myc regulation in chickens, we have completed the structural characterization of the chicken c-myc gene and have begun to investigate c-myc transcription and protein expression. A comparison of c-myc structure and expression between mammals and birds presents an enigma: there...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-06-20 00:00:00
abstract::Bloom syndrome and ataxia-telangiectasia are autosomal recessive human disorders characterized by immunodeficiency, genome instability and predisposition to develop cancer. Recent data reveal that the products of these two genes, BLM and ATM, interact and function together in recognizing abnormal DNA structures. To in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207276
更新日期:2004-02-26 00:00:00
abstract::CCAAT/enhancer-binding protein-δ (C/EBP-δ), a transcription factor, is elevated in carcinoma compared with that in normal tissue. This study reports a novel function of C/EBP-δ in lymphangiogenesis and tumor metastasis. Genetic deletion of C/EBP-δ in mice resulted in a significant reduction of lymphangiogenesis and pu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.187
更新日期:2011-12-08 00:00:00
abstract::We have recently described the N-terminal RAS association domain family of genes, RASSF7-10. Previously, we cloned the N-terminal RASSF10 gene and demonstrated frequent methylation of the associated 5'-CpG island in acute lymphoblastic leukemia. To characterize RASSF10 gene expression, we demonstrate that in developin...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.471
更新日期:2011-02-24 00:00:00
abstract::E2F is a complex family of transcription factors which appears to regulate the transcription of genes required for the S phase of the mammalian cell cycle. In the present work, we have examined the mechanisms regulating E2F-3 accumulation in mouse fibroblasts. We have determined that E2F-3 DNA binding activity is rest...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201633
更新日期:1998-03-12 00:00:00
abstract::The role of p53 in genotoxic therapy-induced metabolic shift in cancers is not yet known. In this study, we investigated the role of p53 in the glycolytic shift in head and neck squamous cell carcinoma cell lines following irradiation. Isogenic p53-null radioresistant cancer cells established through cumulative irradi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0697-6
更新日期:2019-05-01 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