Abstract:
:We have identified a novel mechanism of cross-talk between cell signaling and metabolic pathways, whereby the signaling kinase p21-activated kinase 1 (Pak1) binds to, phosphorylates and enhances the enzymatic activity of phosphoglucomutase 1 (PGM), an important regulatory enzyme in cellular glucose utilization and energy homeostasis. Pak1 and PGM were colocalized in model cell systems and showed functional interactions in a physiological setting. Strong direct interaction of PGM with Pak1 but not Pak2, Pak3, or Pak4 was observed. PGM binding was within 75-149 amino acids (aa) of Pak1, while Pak1 binding to PGM was in the N-terminal 96 aa. Pak1-mediated phosphorylation of PGM selectively on threonine 466 significantly increased PGM enzymatic activity and could be blocked by transfection with a dominant-negative Pak1 expression vector and by Pak1-specific small inhibitory RNA. Stable transfection of PGM into PGM-deficient K562 leukemia cells further demonstrated the role of Pak1 in regulating PGM activity. The results presented here provide new evidence that the cell signaling kinase Pak1 is a novel regulator of glucose metabolism through its phosphorylation and regulation of PGM activity. These findings suggest a new mechanism whereby growth factor signaling may coordinately integrate metabolic regulation with established signaling functions of cell cycle regulation and cell growth.
journal_name
Oncogenejournal_title
Oncogeneauthors
Gururaj A,Barnes CJ,Vadlamudi RK,Kumar Rdoi
10.1038/sj.onc.1207969subject
Has Abstractpub_date
2004-10-21 00:00:00pages
8118-27issue
49eissn
0950-9232issn
1476-5594pii
1207969journal_volume
23pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively control expression of target genes in animals and plants. The microRNA-21 gene (mir-21) has been identified as the only miRNA commonly overexpressed in solid tumors of the lung, breast, stomach, prostate, colon, brain, head and neck, esophagus and pa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.72
更新日期:2008-07-17 00:00:00
abstract::Previous studies have demonstrated a synergistic interaction between rhuMAb HER2 and the cytotoxic drug cisplatin in human breast and ovarian cancer cells. To define the nature of the interaction between rhuMAb HER2 and other classes of cytotoxic drugs, we applied multiple drug effect/combination index (CI) isobologra...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202526
更新日期:1999-04-01 00:00:00
abstract::A potential role for 1-oleoyl-sn-glycero-3-phosphate or lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) in the regulation of malignant diseases has been widely considered. In this study, we found that in transformed astroglial cells, the expression profile of lysophospholipid receptor mRNA and the action...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208805
更新日期:2005-10-06 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and incurable disease. Poor prognosis is due to multiple reasons, including acquisition of resistance to gemcitabine, the first-line chemotherapeutic approach. Thus, there is a strong need for novel therapies, targeting more directly the molecular aberrations of...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.270
更新日期:2016-04-21 00:00:00
abstract::A lot of effort has been done to study how cancer cells react to low-oxygen tension, a condition known as hypoxia. Indeed, abnormal and dysfunctional blood vessels in the tumor are incapable to restore oxygenation, therefore perpetuating hypoxia, which, in turn, will fuel tumor progression, metastasis and resistance t...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2013.121
更新日期:2014-04-03 00:00:00
abstract::The mouse mammary epithelial cell hierarchy contains both multipotent stem cell as well as lineage-limited duct and lobular progenitor cell functions. The latter-also termed parity-identified mammary epithelial cells (PI-MECs)-are marked by beta-galactosidase (β Gal) expression following pregnancy and involution in wh...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.215
更新日期:2012-01-05 00:00:00
abstract::Chromatin remodeling proteins regulate multiple aspects of cell homeostasis, making them ideal candidates for misregulation in transformed cells. Here, we explore Sin3A, a member of the Sin3 family of proteins linked to tumorigenesis that are thought to regulate gene expression through their role as histone deacetylas...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.326
更新日期:2013-06-27 00:00:00
abstract::Persistent infection by high-risk human papillomaviruses (HPVs) is associated with the development of cervical cancer and a subset of anogenital and head and neck squamous cell carcinomas. Abnormal expression of cellular microRNAs (miRNAs) plays an important role in the development of cancer, including HPV-related tum...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-017-0083-1
更新日期:2018-03-01 00:00:00
abstract::Previous studies have documented that Tumor necrosis factor alpha (TNFalpha) is a potent negative regulator of normal hematopoiesis. However, the mechanism by which TNFalpha acts at the cellular level is not totally understood. Although apoptotic cell killing appears to be the most common cellular effect of TNFalpha, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208024
更新日期:2004-09-30 00:00:00
abstract::The identification of target mRNAs is a key step for assessing the role of aberrantly expressed microRNAs in human cancer. MiR-221 is upregulated in human hepatocellular carcinoma (HCC) as well as in other malignancies. One proven target of miR-221 is CDKN1B/p27, whose downregulation affects HCC prognosis. Here, we pr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.178
更新日期:2008-09-25 00:00:00
abstract::Previous studies have shown that the adenovirus E1A oncoprotein can bind to and inactivate the retinoblastoma tumor suppressor protein (pRb) and the transcriptional coactivators CBP/p300. In this study, wild-type E1A12S or two deletion mutants (delN, which binds pRb but not CBP/p300; delCR2, which binds to CBP/p300 bu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205050
更新日期:2002-02-07 00:00:00
abstract::The crizotinib-resistant ALK(F1174L) mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel anaplastic lymphoma kinase (ALK) inhibitors with different modes of action. The diaminopyrimidine TAE684 and its derivative ceritinib (LDK3...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.434
更新日期:2016-07-14 00:00:00
abstract::Inhibitor of DNA-binding (Id) proteins prevent cell differentiation, promote growth and sustain tumour development. They do so by binding to E proteins and other transcription factors through the helix-loop-helix (HLH) domain, and inhibiting transcription. This makes HLH-mediated Id protein interactions an appealing t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.56
更新日期:2009-04-30 00:00:00
abstract::Rearrangements of the NFKB2 gene are associated with lymphoid malignancies, but the functional significance of these alterations is not known. Here we characterize structurally and functionally a rearranged NFKB2 gene identified at the T cell lymphoma line, HUT78. The rearrangement has truncated NFKB2 sequences within...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::Chromosomal translocation t(X;14)(q28;q11) has been observed in patients with pro-lymphocytic T-cell leukaemia (T-PLL). In two cases of T-PLL, one of which was associated with Ataxia telangiectasia (AT), the chromosomal break occurred in two different introns of a gene c6.1A, located at the Xq28 locus. Fusion transcri...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::Wild-type p53 protein displays a spectrum of activities including the ability to suppress transformed cell growth to direct apoptotic cell death and to mediate G1 checkpoint in response to cellular DNA damage. Earlier work showed that a self-association defective p53 protein retained transformation suppressor activity...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::Squamous cell carcinoma (SCC) of the skin represents a group of neoplasms which is associated with exposure to UV light. Recently, we obtained data suggesting that invasive skin cancer and its precursors derive from one original neoplastic clone. Here, the analysis were extended by loss of heterozygosity (LOH) analysi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202080
更新日期:1998-10-08 00:00:00
abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) K13/vFLIP (viral Flice-inhibitory protein) induces transcription of numerous genes through NF-κB activation, including pro-inflammatory cytokines, which contribute to the pathogenesis of Kaposi's sarcoma (KS). In this study, we report that KSHV vFLIP induces the expressio...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.145
更新日期:2013-03-07 00:00:00
abstract::This issue attempts to give a 'state of the art' overview of the AP-1 transcription factor family, a fundamental class of transcriptional regulators. The AP-1 family consists of several bZIP (basic region leucine zipper) domain proteins, the Jun, the Fos, and the ATF subfamilies, which all have to dimerize before they...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204416
更新日期:2001-04-30 00:00:00
abstract::The Src family kinases c-Src, and its downstream effectors, the Rho family of small GTPases RhoA and Jun N-terminal kinase (JNK) have a significant role in tumorigenesis. In this report, using the Drosophila wing disc epithelium as a model system, we demonstrate that the actin-Capping Protein (CP) αβ heterodimer, whic...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.155
更新日期:2014-04-17 00:00:00
abstract::Ewing sarcoma (ES) is an aggressive bone and soft tissue tumor of children and young adults in which finding effective new targeted therapies is imperative. Here, we report an in-depth preclinical study of the investigational cullin-RING ubiquitin ligase (CRL) inhibitor MLN4924 in ES, as we have recently demonstrated ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.153
更新日期:2013-03-14 00:00:00
abstract::The eph gene encodes a putative receptor tyrosine kinase for an as yet unknown ligand. Some human cancer cells have been found to overexpress eph mRNAs without gene amplification. We show here that NIH3T3 cells acquire tumorigenic ability in nude mice and make colonies in soft agar with a viral LTR (Long Terminal Repe...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm. While ATL cells in peripheral blood (PB-ATL) are sensitive to anti-CC chemokine receptor 4 treatment, non-PB-ATLs, including lymph node ATLs (LN-ATLs), are more aggressive and resistant. We examined characteristic cytokines and growth factors that ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01393-x
更新日期:2020-08-01 00:00:00
abstract::In CCL39 cells thrombin is a potent growth factor which requires sustained activation of mitogen activated protein kinases (MAPKs) to promote DNA synthesis. Some of the effects of thrombin can be mimicked by peptides based on the new amino terminus of the cleaved receptor; however, these thrombin receptor peptides (TR...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202647
更新日期:1999-05-20 00:00:00
abstract::A recent large multi-centre study convincingly confirmed previous observations that the SYT-SSX1 fusion type, compared to SYT-SSX2, of synovial sarcoma is associated with a worse clinical outcome. Apart from the clinical impact, this fact also suggests (1) that the SYT-SSX fusion gene may influence molecular mechanism...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205700
更新日期:2002-08-22 00:00:00
abstract::A protein of 300 kDa (p300) associates with the adenovirus E1A proteins and has been implicated in the control of cell cycle progression. In mammalian cells, p300 is actively phosphorylated in both quiescent and proliferating cells and its level of phosphorylation increases as it travels from late G1 into M phase. E1A...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::To clarify the incidence, timing and pathogenetic significance of p53 gene alterations in the progression of small-cell lung carcinoma (SCLC), 17 primary tumors, 13 metastases and nine cell lines from 27 patients were analysed by a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::In order to obtain insight into the parameters determining the subcellular localization of mutant and wild-type forms of p53, we analysed the subcellular distribution of p53 in four Balb/c mouse-derived cell lines ranging in their cellular phenotypes from normal (3T3), via minimal transformant (T3T3), to maximally tra...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::MicroRNAs (miRNAs) make up a novel class of gene regulators; they function as oncogenes or tumor suppressors by targeting tumor-suppressor genes or oncogenes. A recent study that analysed a large number of human cancer cell lines showed that miR-330 is a potential tumor-suppressor gene. However, the function and molec...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.192
更新日期:2009-09-24 00:00:00
abstract::Ultraviolet light (UV) induced DNA lesions efficiently block transcript elongation and induce the p53 response. Although p53 contributes to transcriptional activation of the p21waf1 and bax genes, accumulation of these proteins requires that these genes are free of UV induced pyrimidine dimers. We assessed the level o...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201963
更新日期:1998-08-06 00:00:00