Journal of Biological Chemistry Impact Factor & Information

Publisher: American Society of Biological Chemists; Rockefeller Institute for Medical Research; American Society for Biochemistry and Molecular Biology, American Society for Biochemistry and Molecular Biology

Journal description

Complete content of the Journal of Biological Chemistry as of April 1995.

Current impact factor: 4.57

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 4.573
2013 Impact Factor 4.6
2012 Impact Factor 4.651
2011 Impact Factor 4.773
2010 Impact Factor 5.328
2009 Impact Factor 5.328
2008 Impact Factor 5.52
2007 Impact Factor 5.581
2006 Impact Factor 5.808
2005 Impact Factor 5.854
2004 Impact Factor 6.355
2003 Impact Factor 6.482
2002 Impact Factor 6.696
2001 Impact Factor 7.258
2000 Impact Factor 7.368
1999 Impact Factor 7.666
1998 Impact Factor 7.199
1997 Impact Factor 6.963
1996 Impact Factor 7.452
1995 Impact Factor 7.385
1994 Impact Factor 7.716
1993 Impact Factor 6.793
1992 Impact Factor 6.733

Impact factor over time

Impact factor

Additional details

5-year impact 4.69
Cited half-life >10.0
Immediacy index 0.89
Eigenfactor 0.54
Article influence 1.74
Website Journal of Biological Chemistry website
Other titles The Journal of biological chemistry, JBC
ISSN 0021-9258
OCLC 1782222
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details

American Society for Biochemistry and Molecular Biology

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • Authors accepted peer-reviewed manuscript may be posted on an institutional repository
    • Publisher copyright and source must be acknowledged with set phrase: "This research was originally published in Journal Name. Author(s). Title. Journal Name. Year. Vol:pp-pp. © the American Society for Biochemistry and Molecular Biology"
    • On a non-profit server
    • Publisher's version/PDF cannot be used
  • Classification
    ​ white

Publications in this journal

  • Journal of Biological Chemistry 10/2015; 290(28).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phosphatidylinositol-3,4,5-trisphosphate (PIP3)-dependent Rac exchanger 2 (PREX2) is a guanine nucleotide exchange factor (GEF) for the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase, facilitating the exchange of GDP for GTP on Rac1. GTP bound Rac1 then activates its downstream effectors, including p21 activated kinases (PAK). PREX2 and Rac1 are frequently mutated in cancer, and have key roles within the insulin signaling pathway. Rac1 can be inactivated by multiple mechanisms; however, negative regulation by insulin is not well understood. Here, we show that in response to being activated after insulin stimulation, Rac1 initiates its own inactivation by decreasing PREX2 GEF activity. Following PREX2 mediated activation of Rac1 by the second messengers PIP3 or Gβγ, we found that PREX2 was phosphorylated through a PAK dependent mechanism. PAK mediated phosphorylation of PREX2 reduced GEF activity towards Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ. Cell fractionation experiments also revealed that phosphorylation prevented PREX2 from localizing to the cellular membrane. Further, the onset of insulin induced phosphorylation of PREX2 was delayed compared to AKT. Altogether, we propose that second messengers activate the Rac1 signal, which sets in motion a cascade whereby PAK kinases phosphorylate and negatively regulate PREX2 to decrease Rac1 activation. This type of regulation would allow for transient activation of the PREX2-Rac1 signal, and may be relevant in multiple physiological processes, including diseases such as diabetes and cancer when insulin signaling is chronically activated.
    Journal of Biological Chemistry 10/2015; DOI:10.1074/jbc.M115.668244
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    ABSTRACT: Dietary lipid overload and calorie excess during obesity is a low grade chronic inflammatory state with diminished ability to appropriately metabolize glucose or lipids. Macrophages are critical in maintaining adipose tissue homeostasis, in part by regulating lipid metabolism, energy homeostasis and tissue remodeling. During high fat diet-induced obesity, macrophages are activated by lipid derived "danger signals" such as ceramides and palmitate and promote the adipose tissue inflammation in an Nlrp3 inflammasome-dependent manner. Given that the metabolic fate of fatty acids in macrophages is not entirely elucidated, we have hypothesized that de novo synthesis of ceramide, through the rate-limiting enzyme serine palmitoyltransferase long chain (Sptlc)-2, is required for saturated fatty acid driven Nlrp3 inflammasome activation in macrophages. Here we report that mitochondrial targeted overexpression of catalase which is established to mitigate oxidative stress controls ceramide-induced Nlrp3 inflammasome activation but does not affect the ATP-mediated caspase-1 cleavage. Surprisingly, myeloid cell-specific deletion of Sptlc2 is not required for palmitate driven Nlrp3 inflammasome activation. Furthermore, the ablation of Sptlc2 in macrophages did not impact macrophage polarization or obesity-induced adipose tissue leukocytosis. Consistent with these data, investigation of insulin-resistance using hyperinsulinemic-euglycemic clamps revealed no significant differences in obese mice lacking ceramide de novo synthesis machinery in macrophages. These data suggest that alternate metabolic pathways control fatty acid derived ceramide synthesis in macrophage and the Nlrp3 inflammasome activation in obesity.
    Journal of Biological Chemistry 10/2015; DOI:10.1074/jbc.M115.680199
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    ABSTRACT: Secretion of effector proteins into the eukaryotic host cell is required for Chlamydia trachomatis virulence. In the infection process, Scc1 and Scc4, two chaperones of the type III secretion (T3S) system, facilitate secretion of the important effector and plug protein , CopN, but little is known about the details of this event. Here we use biochemistry, mass spectrometry, nuclear magnetic resonance spectroscopy, and genetic analyses to characterize this trimolecular event. We find that Scc4 complexes with Scc1 and CopN in situ at the late developmental cycle of C. trachomatis. We show that Scc4 and Scc1 undergo dynamic interactions as part of the unique bacterial developmental cycle. Using alanine substitutions, we identify several amino acid residues in Scc4 that are critical for the Scc4·Scc1 interaction, which is required for forming the Scc4·Scc1·CopN ternary complex. These results combined with our previous findings indicating a role in transcription for Scc4 (Rao et al. (2009) Genes Dev 23, 1818), reveal that the T3S process is linked to bacterial transcriptional events, all of which are mediated by Scc4 and its interacting proteins. A model describing how the T3S process may affect gene expression is proposed.
    Journal of Biological Chemistry 10/2015; DOI:10.1074/jbc.M115.670232
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    ABSTRACT: Squalene monooxygenase (SM) is an important control point in cholesterol synthesis beyond 3 hydroxy 3 methylglutaryl CoA reductase (HMGCR). Although it is known to associate with the endoplasmic reticulum (ER), its topology has not been determined. We have elucidated the membrane topology of the sterol-responsive domain of SM, comprising the first 100 amino acids fused to GFP (SM N100-GFP) by determining the accessibility of 16 introduced cysteines to the cysteine-reactive, membrane-impermeable reagent PEG-maleimide (mPEG). We have identified a region integrally associated with the ER membrane that is likely to interact with cholesterol or respond to cholesterol-induced membrane effects. By comparing cysteine accessibility with and without cholesterol treatment, we further present evidence to suggest that cholesterol induces a conformational change in SM N100-GFP. This change is likely to lead to its targeted degradation by the ubiquitin-proteasome system (UPS), since degradation is blunted by treatment with the chemical chaperone glycerol, which retains SM N100-GFP in its native conformation. Furthermore, degradation can be disrupted by insertion of two N-terminal myc tags, implicating the N-terminus in this process. Together, this information provides new molecular insights into the regulation of this critical control point in cholesterol synthesis.
    Journal of Biological Chemistry 10/2015; DOI:10.1074/jbc.M115.675181
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    ABSTRACT: Alteration/Deficiency in Activation 3 (ADA3) is a conserved component of several transcriptional co-activator and histone acetyl transferase (HAT) complexes. Recently, we generated Ada3 knockout mice and demonstrated that deletion of Ada3 leads to early embryonic lethality. Use of Ada3FL/FL mouse embryonic fibroblasts (MEFs) with deletion of Ada3 using adenovirus Cre showed a critical role of ADA3 in cell cycle progression through mitosis. Here, we demonstrate an association of ADA3 with high order repeat (HOR) region of the alpha-satellite region on human X chromosome centromeres that is consistent with its role in mitosis. Given the role of centromere proteins (CENPs) in mitosis, we next analyzed if ADA3 associates with centromere through CENPs. Both in vivo proximity ligation assay and immunofluorescence studies confirmed the association of ADA3 with CENP-B protein, a highly conserved centromeric protein which binds to the 17-bp DNA sequences on alpha-satellite DNA. Deletional analysis showed ADA3 directly associates with CENP-B through its N-terminus and a CENP-B binding deficient mutant of ADA3 was incompetent in cell proliferation rescue. Notably, knockdown of ADA3 decreased binding of CENP-B onto the centromeres, suggesting ADA3 is required for the loading of CENP-B on to the centromeres. Finally, we show that deletion of Ada3 from Ada3FL/FLMEFs exhibited various chromosome segregation defects. Taken together, we demonstrate a novel ADA3 interaction with CENP-B-centromere that may account for its previously known function in mitosis. This study together with its known function in maintaining genomic stability and its mis-localization in cancers, suggests an important role of ADA3 in mitosis.
    Journal of Biological Chemistry 10/2015; DOI:10.1074/jbc.M115.685511
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    ABSTRACT: Precise modulation of histone gene transcription is critical for cell cycle progression. As a direct substrate of Cyclin E/CDK2, NPAT is a crucial factor in regulating histone transcription and cell cycle progression. Here we identified that the Cpn10/HSPE, a 10KD heat shock protein, is a novel interacting partner of NPAT. A pool of Cpn10 is colocalized with NPAT foci in nuclei. Gain- and loss-of-function experiments unraveled an essential role of Cpn10 in histone transcription. A conserved DLFD motif within Cpn10 was critical for targeting NPAT and modulating histone transcription. More importantly, knockdown of Cpn10 disrupted the foci formation of both NPAT and FLASH without affecting Coilin-positive Cajal bodies. Finally, Cpn10 is important for S-phase progression and cell proliferation. Taken together, our finding revealed a novel role of Cpn10 in the spatial regulation of NPAT signaling and disclosed a previously unappreciated linkage between the heat shock protein and histone transcription regulation.
    Journal of Biological Chemistry 10/2015; DOI:10.1074/jbc.M115.659201
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    ABSTRACT: Syk is a cytoplasmic kinase that serves multiple functions within the immune system to couple receptors for antigens and antigen-antibody complexes to adaptive and innate immune responses. Recent studies have identified additional roles for the kinase in cancer cells where its expression can either promote or suppress tumor cell growth depending on the context. Proteomic analyses of Syk-binding proteins identified several interacting partners also found to be recruited to stress granules. We show here that the treatment of cells with inducers of stress granule formation leads to the recruitment of Syk to these protein-RNA complexes. This recruitment requires the phosphorylation of Syk on tyrosine and results in the phosphorylation of proteins at or near the stress granule. Grb7 is identified as a Syk-binding protein involved in the recruitment of Syk to the stress granule. This recruitment promotes the formation of autophagosomes and the clearance of stress granules from the cell once the stress is relieved, enhancing the ability of cells to survive the stress stimulus.
    Journal of Biological Chemistry 10/2015; DOI:10.1074/jbc.M115.642900
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    ABSTRACT: Poly(ADP-ribose) polymerase-1 (PARP-1) is an ADP-ribosylating enzyme participating in diverse cellular functions. The roles of PARP-1 in the immune system, however, have not been well understood. Here we find that PARP-1 interacts with FOXP3 and induces its poly(ADP-ribosyl)ation. By using PARP-1 inhibitors, we show that reduced poly(ADP-ribosyl)ation of FOXP3 results in not only FOXP3 stabilization and increased FOXP3 downstream genes, but also enhanced suppressive function of regulatory T cells (Treg). Our results suggest that PARP-1 negatively regulates the suppressive function of Treg cells at the post-translational level via FOXP3 poly(ADP-ribosyl)ation. This finding has implications in developing PARP-1 inhibitors as potential agents for the prevention and treatment of autoimmune diseases.
    Journal of Biological Chemistry 10/2015; DOI:10.1074/jbc.M115.661611
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    ABSTRACT: Calsequestrin 1 (hCasq1) is the principal Ca(2+) storage protein of the sarcoplasmic reticulum of skeletal muscle. Its inheritable D244G mutation causes a myopathy with vacuolar aggregates, while its M87T variant is weakly associated with malignant hyperthermia (MH). We characterized the consequences of these mutations with studies of the human proteins in vitro. Equilibrium dialysis and turbidity measurements showed that D244G and, to a lesser extent, M87T partially lose Ca(2+) binding exhibited by wild type hCasq1 at high Ca(2+) concentrations. D244G aggregates abruptly and abnormally, a property that fully explains the protein inclusions that characterize its phenotype. D244G crystallized in low Ca(2+) concentrations lacks two Ca(2+) ions normally present in wild type, which weakens the hydrophobic core of Domain II. D244G crystallized in high Ca(2+) concentrations regains its missing ions and Domain II order, but shows a novel dimeric interaction. The M87T mutation causes a major shift of the α-helix bearing the mutated residue, significantly weakening the back-to-back interface essential for tetramerization. D244G exhibited the more severe structural and biophysical property changes, which matches the different pathophysiological impacts of these mutations.
    Journal of Biological Chemistry 09/2015; DOI:10.1074/jbc.M115.686261
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    ABSTRACT: Bacterial pore-forming toxins (PFTs) are structurally diverse pathogen-secreted proteins that form cell-damaging channels in the membranes of host cells. Most PFTs are released as water-soluble monomers that first oligomerize on the membrane before inserting a transmembrane channel. To modulate specificity and increase potency, many PFTs recognize specific cell-surface receptors that increase the local toxin concentration on cell membranes thereby facilitating channel formation. Vibrio cholerae cytolysin (VCC) is a toxin secreted by the human pathogen responsible for pandemic cholera disease and acts as a defensive agent against the host immune system. While it has been shown that VCC utilizes specific glycan receptors on the cell surface, additional direct contacts with the membrane must also play a role in toxin binding. To better understand the nature of these interactions, we conducted a systematic investigation of the membrane-binding surface of VCC to identify additional membrane interactions important in cell targeting. Through cell-based assays on several human-derived cell-lines we show that VCC is unlikely to utilize high-affinity protein receptors like structurally similar toxins from Staphylococcus aureus. Next, we identified a number of specific amino-acid residues that greatly diminish the VCC potency against cells and investigated the interplay between glycan-binding and these direct lipid contacts. Finally, we used model membranes to parse the importance of these key residues in lipid and cholesterol binding. Our study provides a complete functional map of the VCC membrane-binding surface and insights into the integration of sugar, lipid, and cholesterol binding-interactions.
    Journal of Biological Chemistry 09/2015; DOI:10.1074/jbc.M115.675967
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    ABSTRACT: Efficient immune responses require regulated antigen presentation to CD4 T cells. IL-10 inhibits the ability of DCs and macrophages to stimulate antigen-specific CD4 T cells, however the mechanisms by which IL-10 suppresses antigen presentation remain poorly understood. We now report that IL-10 stimulates expression of the E3 ubiquitin-ligase March-I in activated macrophages, thereby down-regulating MHC-II, CD86, and antigen presentation to CD4 T cells. By contrast, IL-10 does not stimulate March-I expression in DCs, does not suppress MHC-II or CD86 expression on either resting or activated DCs, and does not affect antigen presentation by activated DCs. IL-10 does, however, inhibit the process of DC activation itself, thereby reducing the efficiency of antigen presentation in a March-I-independent manner. Thus, IL-10 suppression of APC function in macrophages is March-I-dependent whereas in DCs suppression is March-I-independent.
    Journal of Biological Chemistry 09/2015;
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    ABSTRACT: The RAVE complex (regulator of the H+-ATPase of vacuolar and endosomal mem-branes) is required for biosynthetic assembly and glucose-stimulated reassembly of the yeast vacuolar H+-ATPase (V-ATPase). Yeast RAVE contains three subunits, Rav1, Rav2 and Skp1. Rav1 is the largest subunit, and it binds Rav2 and Skp1 of RAVE, the E, G, and C subunits of the V-ATPase peripheral V1 sector and Vph1 of the membrane Vo sector. We identified Rav1 regions required for interaction with its binding partners through deletion analysis, co-immunoprecipitation, two-hybrid assay, and pull-down assays with expressed proteins. We find that Skp1 binding requires sequences near the C-terminus of Rav1, V1 subunits E and C bind to a conserved region in the C-terminal half of Rav1, and the cytosolic domain of Vph1 binds near the junction of the Rav1 N- and C-terminal halves. In contrast, Rav2 binds to the N-terminal domain of Rav1, which can be modeled as a double β-propeller. Only the V1 C subunit binds to both Rav1 and Rav2. Using GFP-tagged RAVE subunits in vivo, we demonstrate glucose-dependent association of RAVE with the vacuolar membrane, consistent with its role in glucose-dependent V-ATPase assembly. It is known that V1 subunit C localizes to the V1-Vo interface in assembled V-ATPase complexes and is important in regulated disassembly of V-ATPases. We propose that RAVE cycles between cytosol and vacuolar membrane in a glucose-dependent manner, positioning V1 and V0 subcomplexes and orienting the V1 C subunit to promote assembly.
    Journal of Biological Chemistry 09/2015; DOI:10.1074/jbc.M115.667634
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    ABSTRACT: The digestive function of the stomach depends on acidification of the gastric lumen. Acid secretion into the lumen is triggered by activation of PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. A coupling protein is ezrin whose phosphorylation at Ser66 by PKA is required for parietal cell activation. However, little is known regarding the molecular mechanism(s) by which this signaling pathway operates in gastric acid secretion. Here we show PKA cooperates with MST4 to orchestrate histamine-elicited acid secretion by phosphorylating ezrin at Ser66 and Thr567, respectively. Histamine stimulation activates PKA which phosphorylates MST4 at Thr178 and then promotes MST4 kinase activity. Interestingly, activated MST4 then phosphorylates ezrin pre-phosphorylated by PKA. Importantly, MST4 is important for acid secretion in parietal cells because either suppression of MST4 or overexpression of non-phosphorylatable MST4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, overexpressing MST4 phosphorylation-deficient ezrin results in an inhibition of gastric acid secretion. Taken together, these results define a novel molecular mechanism linking PKA-MST4-ezrin signaling cascade to polarized epithelial secretion in gastric parietal cells.
    Journal of Biological Chemistry 09/2015; DOI:10.1074/jbc.M115.668855