Abstract:
:Janus kinases are essential for signal transduction by a variety of cytokine receptors and when inappropriately activated can cause hematopoietic disorders and oncogenesis. Consequently, it can be predicted that the interaction of the kinases with receptors and the events required for activation are highly controlled. In a screen to identify phosphorylation events regulating Jak2 activity in EpoR signaling, we identified a mutant (Jak2-Y613E) which has the property of being constitutively activated, as well as an inactivating mutation (Y766E). Although no evidence was obtained to indicate that either site is phosphorylated in signaling, the consequences of the Y613E mutation are similar to those observed with recently described activating mutations in Jak2 (Jak2-V617F and Jak2-L611S). However, unlike the V617F or L611S mutant, the Y613E mutant requires the presence of the receptor but not Epo stimulation for activation and downstream signaling. The properties of the Jak2-Y613E mutant suggest that under normal conditions, Jak2 that is not associated with a receptor is locked into an inactive state and receptor binding through the FERM domain relieves steric constraints, allowing the potential to be activated with receptor engagement.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Funakoshi-Tago M,Pelletier S,Moritake H,Parganas E,Ihle JNdoi
10.1128/MCB.01447-07subject
Has Abstractpub_date
2008-03-01 00:00:00pages
1792-801issue
5eissn
0270-7306issn
1098-5549pii
MCB.01447-07journal_volume
28pub_type
杂志文章abstract::The heterochromatic domains of Drosophila melanogaster (pericentric heterochromatin, telomeres, and the fourth chromosome) are characterized by histone hypoacetylation, high levels of histone H3 methylated on lysine 9 (H3-mK9), and association with heterochromatin protein 1 (HP1). While the specific interaction of HP1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.18.8210-8220.2004
更新日期:2004-09-01 00:00:00
abstract::Processing from pre-mRNA introns is a widespread mechanism to generate human box C/D and H/ACA snoRNAs. Recent studies revealed that an optimal position relative to the 3' splice site is important for efficient processing of most box C/D snoRNAs and that assembly of box C/D snoRNPs is stimulated by splicing factors li...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.7.2540-2549.2006
更新日期:2006-04-01 00:00:00
abstract::Previously we demonstrated that the heat shock transcription factor Hsf1 is indispensable for transformation of mammary epithelial cells by the Her2 oncogene. Since Hsf1 affects oncogene-induced senescence (OIS), these findings suggest that Hsf1 affects tumor initiation when OIS plays a role. Indeed, here we report th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05921-11
更新日期:2012-03-01 00:00:00
abstract::Saccharomyces cerevisiae dbf4 and cdc7 cell cycle mutants block initiation of DNA synthesis (i.e., are iDS mutants) at 37 degrees C and arrest the cell cycle with a 1C DNA content. Surprisingly, certain dbf4 and cdc7 strains divide their chromatin at 37 degrees C. We found that the activation of the Cdc28 mitotic prot...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.10.5312
更新日期:1995-10-01 00:00:00
abstract::Interleukin-5 (IL-5) and IL-6 have both been reported to act as B-cell differentiation factors by stimulating activated B cells to secrete antibody. However, it has not been possible to directly compare the effects of these two lymphokines because of the lack of a suitable B-cell line capable of responding to both. We...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.7.3929
更新日期:1993-07-01 00:00:00
abstract::To examine a role for focal adhesion kinase (FAK) in cardiac morphogenesis, we generated a line of mice with a conditional deletion of FAK in nkx2-5-expressing cells (herein termed FAKnk mice). FAKnk mice died shortly after birth, likely resulting from a profound subaortic ventricular septal defect and associated mala...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00068-07
更新日期:2007-08-01 00:00:00
abstract::In the yeast Saccharomyces cerevisiae, yeast RAS proteins are potent activators of adenylate cyclase. In the present work we measured the activity of adenylate cyclase in membranes from Saccharomyces cerevisiae which overexpress this enzyme. The response of the enzyme to added RAS2 proteins bound with various guanine ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.6.2128
更新日期:1987-06-01 00:00:00
abstract::Telomerase is a ribonucleoprotein enzyme that adds repetitive sequences to the ends of linear chromosomes, thereby counteracting nucleotide loss due to incomplete replication. A short region of the telomerase RNA subunit serves as template for nucleotide addition onto the telomere 3' end. Although Saccharomyces cerevi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.21.7277-7286.2001
更新日期:2001-11-01 00:00:00
abstract::The int-1 proto-oncogene is a target for insertional activation of transcription by mouse mammary tumor virus in many murine mammary tumors. Whereas no expression of int-1 is seen in normal mammary tissue, int-1 RNA can be detected in normal mice in the neural tubes of midgestation embryos and in postmeiotic spermatoc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.8.3377
更新日期:1989-08-01 00:00:00
abstract::We studied RNA polymerase I transcription in cells transfected with a plasmid, prHuTK, containing the herpes simplex virus tk gene fused to a human rRNA promoter. Primer extension analysis of tk RNA isolated from COS cells transfected with prHuTK reveals that transcription from the RNA polymerase I promoter is highly ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.2.352
更新日期:1985-02-01 00:00:00
abstract::Sortilin is a member of the Vps10p domain family of neuropeptide and neurotrophin binding neuronal receptors. The family members interact with and partly share a variety of ligands and partake in intracellular sorting and protein transport as well as in transmembrane signal transduction. Thus, sortilin mediates the tr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00274-10
更新日期:2010-09-01 00:00:00
abstract::Exchange proteins activated by cAMP (cyclic AMP) 2 (Epac2) is a guanine nucleotide exchange factor for Rap1, a small G protein involved in many cellular functions, including cell adhesion, differentiation, and exocytosis. Epac2 interacts with Ras-GTP via a Ras association (RA) domain. Previous studies have suggested t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01060-08
更新日期:2008-12-01 00:00:00
abstract::Reduction of the survival of motor neurons (SMN) protein levels causes the motor neuron degenerative disease spinal muscular atrophy, the severity of which correlates with the extent of reduction in SMN. SMN, together with Gemins 2 to 7, forms a complex that functions in the assembly of small nuclear ribonucleoprotein...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.13.5543-5551.2005
更新日期:2005-07-01 00:00:00
abstract::The male-specific-lethal (MSL) proteins in Drosophila melanogaster serve to adjust gene expression levels in male flies containing a single X chromosome to equal those in females with a double dose of X-linked genes. Together with noncoding roX RNA, MSL proteins form the "dosage compensation complex" (DCC), which inte...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.14.5947-5954.2005
更新日期:2005-07-01 00:00:00
abstract::RNA-dependent RNA polymerase (RdRP) plays key roles in RNA silencing to generate double-stranded RNAs. In model organisms, such as Caenorhabditis elegans and Neurospora crassa, two types of small interfering RNAs (siRNAs), primary siRNAs and secondary siRNAs, are expressed; RdRP produces secondary siRNAs de novo, with...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01021-15
更新日期:2016-03-31 00:00:00
abstract::The Fanconi anemia (FA) pathway is a DNA damage-activated signaling pathway which regulates cellular resistance to DNA cross-linking agents. Cloned FA genes and proteins cooperate in this pathway, and monoubiquitination of FANCD2 is a critical downstream event. The cell cycle checkpoint kinase ATR is required for the ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02018-05
更新日期:2006-09-01 00:00:00
abstract::PGC-1α is a key transcription coactivator regulating energy metabolism in a tissue-specific manner. PGC-1α expression is tightly regulated, it is a highly labile protein, and it interacts with various proteins--the known attributes of intrinsically disordered proteins (IDPs). In this study, we characterize PGC-1α as a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01672-12
更新日期:2013-07-01 00:00:00
abstract::To distinguish among possible mechanisms of repair of a double-strand break (DSB) by gene conversion in budding yeast, Saccharomyces cerevisiae, we employed isotope density transfer to analyze budding yeast mating type (MAT) gene switching in G2/M-arrested cells. Both of the newly synthesized DNA strands created durin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01654-06
更新日期:2006-12-01 00:00:00
abstract::During mammalian dosage compensation, one of two X-chromosomes in female cells is inactivated. The choice of which X is silenced can be imprinted or stochastic. Although genetic loci influencing the choice decision have been identified, the primary marks for imprinting and random selection remain undefined. Here, we e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.6.2109-2117.2006
更新日期:2006-03-01 00:00:00
abstract::In mast cells, antigen-mediated aggregation of the high-affinity receptor for immunoglobulin E, Fc epsilon RI, stimulates tyrosine phosphorylation and activation of multiple signaling pathways leading to the release of several classes of mediators of the allergic response. Early events induced upon cross-linking of Fc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.3.1582
更新日期:1995-03-01 00:00:00
abstract::Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act sy...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.11.7546
更新日期:1994-11-01 00:00:00
abstract::The DNA single-strand break repair (SSBR) protein XRCC1 is required for genetic stability and for embryonic viability. XRCC1 possesses two BRCA1 carboxyl-terminal (BRCT) protein interaction domains, denoted BRCT I and II. BRCT II is required for SSBR during G(1) but is dispensable for this process during S/G(2) and co...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.8.2556-2563.2002
更新日期:2002-04-01 00:00:00
abstract::Transcriptional activators interact with multisubunit coactivators that modify chromatin structure or recruit the general transcriptional machinery to their target genes. Budding yeast cells respond to amino acid starvation by inducing an activator of amino acid biosynthetic genes, Gcn4p. We conducted a comprehensive ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.8.2800-2820.2003
更新日期:2003-04-01 00:00:00
abstract::Epidermal growth factor (EGF) receptor (EGFR) has been implicated in tumor development and invasion. Dimerization and autophosphorylation of EGFR are the critical events for EGFR activation. However, the regulation of EGF-dependent and EGF-independent dimerization and phosphorylation of EGFR has not been fully underst...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00758-14
更新日期:2014-10-01 00:00:00
abstract::We characterized the organization and expression of PHO5 and PHO3, the tightly linked repressible and constitutive acid phosphatase genes of Saccharomyces cerevisiae. The "constitutive" gene, PHO3, is expressed only when PHO5 is not. Altering PHO5 expression, either through promoter deletions or through mutations in t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.6.1855
更新日期:1986-06-01 00:00:00
abstract::Studies were performed to verify the physiological significance of attenuation in the life cycle of simian virus 40 and the role of agnoprotein in this process. For these purposes, nuclei were isolated at various times after infection and incubated in vitro in the presence of [alpha-32P]UTP under the standard conditio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.6.1327
更新日期:1985-06-01 00:00:00
abstract::The pancreatic-islet-enriched transcription factors MafA and MafB have unique expression patterns in β cells in rodents. MafA is specifically expressed in β cells and is a key regulatory factor for maintaining adult β-cell function, whereas MafB plays an essential role in β-cell development during embryogenesis, and i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00080-19
更新日期:2019-08-12 00:00:00
abstract::The Polycomb group proteins are involved in maintenance of the silenced state of several developmentally regulated genes. These proteins form large aggregates with different subunit compositions. To explore the nature of these complexes and their function, we used the full-length Eed (embryonic ectoderm development) p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.10.5634
更新日期:1998-10-01 00:00:00
abstract::Drosophila sine oculis and eyes absent genes synergize in compound-eye formation. The murine homologues of these genes, Six and Eya, respectively, show overlapping expression patterns during development. We hypothesized that Six and Eya proteins cooperate to regulate their target genes. Cotransfection assays were perf...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.6815
更新日期:1999-10-01 00:00:00
abstract::B-lymphocyte development requires the basic helix-loop-helix proteins encoded by the E2A gene. In this study, the control mechanism of E2A was further explored by disruption of the E2A-related genes, E2-2 and HEB. In contrast to E2A, E2-2 and HEB are not essential for the establishment of the B-cell lineage. However, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.6.2898
更新日期:1996-06-01 00:00:00