Abstract:
:The intracellular signaling mechanisms underlying the pathogenesis of cardiac diseases are not fully understood. We report here that selective deletion of Shp2, an SH2-containing cytoplasmic tyrosine phosphatase, in striated muscle results in severe dilated cardiomyopathy in mice, leading to heart failure and premature mortality. Development of cardiomyopathy in this mouse model is coupled with insulin resistance, glucose intolerance, and impaired glucose uptake in striated muscle cells. Shp2 deficiency leads to upregulation of leukemia inhibitory factor-stimulated phosphatidylinositol 3-kinase/Akt, Erk5, and Stat3 pathways in cardiomyocytes. Insulin resistance and impaired glucose uptake in Shp2-deficient mice are at least in part due to impaired protein kinase C-zeta/lambda and AMP-kinase activities in striated muscle. Thus, we have generated a mouse line modeling human patients suffering from cardiomyopathy and insulin resistance. This study reinforces a concept that a compound disease with multiple cardiovascular and metabolic disturbances can be caused by a defect in a single molecule such as Shp2, which modulates multiple signaling pathways initiated by cytokines and hormones.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Princen F,Bard E,Sheikh F,Zhang SS,Wang J,Zago WM,Wu D,Trelles RD,Bailly-Maitre B,Kahn CR,Chen Y,Reed JC,Tong GG,Mercola M,Chen J,Feng GSdoi
10.1128/MCB.01661-08subject
Has Abstractpub_date
2009-01-01 00:00:00pages
378-88issue
2eissn
0270-7306issn
1098-5549pii
MCB.01661-08journal_volume
29pub_type
杂志文章abstract::The K-fgf/hst oncogene encodes a secreted growth factor of the fibroblast growth factor (FGF) family. The ability of K-fgf-transformed cells to grow in soft agar and in serum-free medium is inhibited by anti-K-FGF neutralizing antibodies, consistent with an autocrine mechanism of transformation. The transformed proper...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.2.1138
更新日期:1991-02-01 00:00:00
abstract::Csn3 (Cops3) maps to the mouse chromosome 11 region syntenic to the common deletion interval for the Smith-Magenis syndrome, a contiguous gene deletion syndrome. It encodes the third subunit of an eight-subunit protein complex, the COP9 signalosome (CSN), which controls a wide variety of molecules of different functio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.19.6798-6808.2003
更新日期:2003-10-01 00:00:00
abstract::Growth, patterning, and apoptosis are mutually interactive during development. For example, cells that select an abnormal fate in a developing field are frequently removed by apoptosis. An important issue in this process that needs to be resolved is the mechanism used by cells to discern their correct fate from an abn...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.8.3140-3150.2005
更新日期:2005-04-01 00:00:00
abstract::Retinoid X receptors (RXR) have been identified as common subunits in the regulation of multiple hormonal signaling pathways. Using circular permutation and phasing analysis of specific response elements, we present evidence that RXR-retinoic acid receptor and RXR-thyroid hormone receptor heterodimer or RXR-RXR homodi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.10.6509
更新日期:1993-10-01 00:00:00
abstract::The proteins encoded by both viral and cellular forms of the c-myc oncogene have been previously demonstrated to have exceptionally short in vivo half-lives. In this paper we report a comparative study on the parameters affecting turnover of nuclear oncoproteins c-myc, c-myb, and the rapidly metabolized cytoplasmic en...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.6.2504
更新日期:1988-06-01 00:00:00
abstract::Mutants of Saccharomyces cerevisiae that lack vacuolar proton-translocating ATPase (V-ATPase) activity show a well-defined set of Vma- (stands for vacuolar membrane ATPase activity) phenotypes that include pH-conditional growth, increased calcium sensitivity, and the inability to grow on nonfermentable carbon sources....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.3.1534
更新日期:1998-03-01 00:00:00
abstract::Gradients of Wnt/beta-catenin signaling coordinate development and physiological homeostasis in metazoan animals. Proper embryonic development of the fruit fly Drosophila melanogaster requires the Naked cuticle (Nkd) protein to attenuate a gradient of Wnt/beta-catenin signaling across each segmental anlage. Nkd inhibi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00133-07
更新日期:2007-06-01 00:00:00
abstract::The rad18 gene of Schizosaccharomyces pombe is an essential gene that is involved in several different DNA repair processes. Rad18 (Smc6) is a member of the structural maintenance of chromosomes (SMC) family and, together with its SMC partner Spr18 (Smc5), forms the core of a high-molecular-weight complex. We show her...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.1.172-184.2005
更新日期:2005-01-01 00:00:00
abstract::Cks1 is an activator of the SCF(Skp2) ubiquitin ligase complex that targets the cell cycle inhibitor p27(Kip1) for degradation. The loss of Cks1 results in p27(Kip1) accumulation and decreased proliferation and inhibits tumorigenesis. We identify here a function of Cks1 in mammalian cell cycle regulation that is indep...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06771-11
更新日期:2012-07-01 00:00:00
abstract::The action of insulin to recruit the intracellular GLUT4 glucose transporter to the plasma membrane of 3T3-L1 adipocytes is mimicked by endothelin 1, which signals through trimeric G(alpha)q or G(alpha)11 proteins. Here we report that murine G(alpha)11 is most abundant in fat and that expression of the constitutively ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.15.5262-5275.2001
更新日期:2001-08-01 00:00:00
abstract::The G2-to-M transition (or prophase) checkpoint of the cell cycle is a critical regulator of mitotic entry. SIRT2, a tumor suppressor gene, contributes to the control of this checkpoint by blocking mitotic entry under cellular stress. However, the mechanism underlying both SIRT2 activation and regulation of the G2-to-...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00184-15
更新日期:2015-11-01 00:00:00
abstract::Oxygen-dependent proteolysis is the primary means of regulating the hypoxia-inducible factor (HIF) family of transcription factors. The alpha-subunit of HIF factor 1 (HIF-1) contains two highly conserved oxygen-dependent degradation domains (402 ODD and 564 ODD), each of which includes a proline that is hydroxylated i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.15.6415-6426.2005
更新日期:2005-08-01 00:00:00
abstract::ABFI (ARS-binding protein I) is a yeast protein that binds specific DNA sequences associated with several autonomously replicating sequences (ARSs). ABFI also binds sequences located in promoter regions of some yeast genes, including DED1, an essential gene of unknown function that is transcribed constitutively at a h...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.3.887
更新日期:1990-03-01 00:00:00
abstract::The RBP-J/Su(H) DNA-binding protein plays a key role in transcriptional regulation by targeting Epstein-Barr virus nuclear antigen 2 (EBNA2) and the intracellular portions of Notch receptors to specific promoters. Using the yeast two-hybrid system, we isolated a LIM-only protein, KyoT, which physically interacts with ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.1.644
更新日期:1998-01-01 00:00:00
abstract::Activation of multiple signaling pathways is required to trigger the full spectrum of in vitro and in vivo phenotypic traits associated with neoplastic transformation by oncogenic Ras. To determine which of these pathways are important for N-ras tumorigenesis in human cancer cells and also to investigate the possibili...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.24.9294-9306.2000
更新日期:2000-12-01 00:00:00
abstract::Numb proteins are evolutionarily conserved signaling molecules that make the daughter cells different after asymmetric divisions by segregating to only one daughter. They contain distinct binding motifs for alpha-adaptin (alpha-Ada) and proteins with Eps15 homology (EH) domains, which regulate endocytosis, and for E3 ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.8.2899-2909.2005
更新日期:2005-04-01 00:00:00
abstract::Human myeloid leukemia cells respond to 12-O-tetradecanoylphorbol-13-acetate (TPA) and other activators of protein kinase C (PKC) with induction of monocytic differentiation. The present studies demonstrated that treatment of U-937 and HL-60 myeloid leukemia cells with TPA, phorbol-12,13-dibutyrate, or bryostatin 1 wa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.1.461
更新日期:1999-01-01 00:00:00
abstract::Fibroblasts transformed by Fos oncogenes display increased expression of a number of genes implicated in tumor cell invasion and metastasis. In contrast to normal 208F rat fibroblasts, Fos-transformed 208F fibroblasts are growth factor independent for invasion. We demonstrate that invasion of v-Fos- or epidermal growt...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.2.963
更新日期:1997-02-01 00:00:00
abstract::We reported the identification of a new family of DNA-binding proteins from our characterization of the dead ringer (dri) gene of Drosophila melanogaster. We show that dri encodes a nuclear protein that contains a sequence-specific DNA-binding domain that bears no similarity to known DNA-binding domains. A number of p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.3.792
更新日期:1996-03-01 00:00:00
abstract::Recruitment of modifiers and remodelers to specific DNA sites within chromatin plays a critical role in controlling gene expression. The study of globin gene regulation provides a convergence point within which to address these issues in the context of tissue-specific and developmentally regulated expression. In this ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.7.2413-2422.2001
更新日期:2001-04-01 00:00:00
abstract::NMYC is a gene whose amplification and overexpression have been implicated in the generation of certain human malignancies. Little is known of how the expression of NMYC is normally controlled. We have therefore characterized transcription from the gene and the structure and stability of the resulting mRNAs. Transcrip...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.12.4266
更新日期:1987-12-01 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::SWI-SNF is an ATP-dependent chromatin remodeling complex that disrupts DNA-histone interactions. Several studies of SWI-SNF activity on mononucleosome substrates have suggested that remodeling leads to novel, accessible nucleosomes which persist in the absence of continuous ATP hydrolysis. In contrast, we have reporte...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.9.3058-3068.2000
更新日期:2000-05-01 00:00:00
abstract::Intracisternal A-particle (IAP) sequences are endogenous retrovirus-like mobile elements, or retrotransposons, present at 1,000 copies in the mouse genome. These elements transpose in a replicative manner via an RNA intermediate and its reverse transcription, and their transposition should therefore be tightly control...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.8.4495
更新日期:1996-08-01 00:00:00
abstract::In vitro studies have implicated nuclear respiratory factor 1 (NRF-1) in the transcriptional expression of nuclear genes required for mitochondrial respiratory function, as well as for other fundamental cellular activities. We investigated here the in vivo function of NRF-1 in mammals by disrupting the gene in mice. A...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.2.644-654.2001
更新日期:2001-01-01 00:00:00
abstract::Major histocompatibility complex class II (MHCII) molecules play a pivotal role in the immune system because they direct the development and activation of CD4(+) T cells. There are three human MHCII isotypes, HLA-DR, HLA-DQ, and HLA-DP. Key transcription factors controlling MHCII genes have been identified by virtue o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.21.17.5699-5709.2001
更新日期:2001-09-01 00:00:00
abstract::The female-sterile ovarian tumor gene, otu, is located in cytological region 7F1 on the Drosophila melanogaster chromosome map. We have mapped the gene at the molecular level by using four dysgenic alleles and two revertant derivatives of these alleles as well as an ethyl methanesulfonate-induced allele. The insertion...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.4.1481
更新日期:1988-04-01 00:00:00
abstract::FUD6, a nonphotosynthetic mutant of Chlamydomonas reinhardtii, was previously found to be deficient in the synthesis of subunit IV of the cytochrome b6/f complex, the chloroplast petD gene product (C. Lemaire, J. Girard-Bascou, F.-A. Wollman, and P. Bennoun, Biochim. Biophys. Acta 851:229-238, 1986). The lesion in FUD...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.6171
更新日期:1994-09-01 00:00:00
abstract::The tumor suppressor WT1 represses and activates transcription. The loss and/or imbalance of the dual transcriptional activity of WT1 may contribute to Wilms' tumor. In this study, we identified par-4 (for prostate apoptosis response) as a WT1-interacting protein that itself functions as a transcriptional repressor. p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.12.6945
更新日期:1996-12-01 00:00:00
abstract::We have previously identified an 11-base DNA sequence, 5'-G-G-T-A-C-C-T-A-A-C-C-3' (simian virus 40 [SV40] map position 294 to 304), which is important in the control of SV40 late RNA expression in vitro and in vivo (Brady et al., Cell 31:625-633, 1982). We report here the identification of another domain of the SV40 ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.1.133
更新日期:1984-01-01 00:00:00