Growth-factor receptor-bound protein-2 (Grb2) signaling in B cells controls lymphoid follicle organization and germinal center reaction.
AuthorsJang IK, Cronshaw DG, Xie LK, Fang G, Zhang J, Oh H, Fu YX, Gu H, Zou Y
JournalProc Natl Acad Sci U S A
PubMed ID21508326
'Grb2 (growth-factor receptor-bound protein-2) is a signaling adaptor that interacts with numerous receptors and intracellular signaling molecules. However, its role in B-cell development and function remains unknown. Here we show that ablation of Grb2 in B cells results in enhanced B-cell receptor signaling; however, mutant B cells do not form ... More
Hyaluronan-mediated CD44 interaction with RhoGEF and Rho kinase promotes Grb2-associated binder-1 phosphorylation and phosphatidylinositol 3-kinase signaling leading to cytokine (macrophage-colony stimulating factor) production and breast tumor progression.
'In this study we have examined CD44 (a hyaluronan (HA) receptor) interaction with a RhoA-specific guanine nucleotide exchange factor (p115RhoGEF) in human metastatic breast tumor cells (MDA-MB-231 cell line). Immunoprecipitation and immunoblot analyses indicate that both CD44 and p115RhoGEF are expressed in MDA-MB-231 cells and that these two proteins are ... More
Changes in the mitochondrial phosphoproteome during mammalian hibernation.
AuthorsChung DJ, Szyszka B, Brown JC, Hüner NP, Staples JF,
JournalPhysiol Genomics
PubMed ID23572536
'Mammalian hibernation involves periods of substantial suppression of metabolic rate (torpor) allowing energy conservation during winter. In thirteen-lined ground squirrels (Ictidomys tridecemlineatus), suppression of liver mitochondrial respiration during entrance into torpor occurs rapidly (within 2 h) before core body temperature falls below 30°C, whereas reversal of this suppression occurs slowly ... More
Elevated expression of TANK-binding kinase 1 enhances tamoxifen resistance in breast cancer.
AuthorsWei C, Cao Y, Yang X, Zheng Z, Guan K, Wang Q, Tai Y, Zhang Y, Ma S, Cao Y, Ge X, Xu C, Li J, Yan H, Ling Y, Song T, Zhu L, Zhang B, Xu Q, Hu C, Bian XW, He X, Zhong H,
Journal
PubMed ID24449872
'Resistance to antiestrogens is one of the major challenges in breast cancer treatment. Although phosphorylation of estrogen receptor a (ERa) is an important factor in endocrine resistance, the contributions of specific kinases in endocrine resistance are still not fully understood. Here, we report that an important innate immune response kinase, ... More
Oxysterols inhibit phosphatidylcholine synthesis via ERK docking and phosphorylation of CTP:phosphocholine cytidylyltransferase.
AuthorsAgassandian M, Zhou J, Tephly LA, Ryan AJ, Carter AB, Mallampalli RK,
JournalJ Biol Chem
PubMed ID15788406
Surfactant deficiency contributes to acute lung injury and may result from the elaboration of bioactive lipids such as oxysterols. We observed that the oxysterol 22-hydroxycholesterol (22-HC) in combination with its obligate partner, 9-cis-retinoic acid (9-cis-RA), decreased surfactant phosphatidylcholine (PtdCho) synthesis by increasing phosphorylation of the regulatory enzyme CTP:phosphocholine cytidylyltransferase-alpha (CCTalpha). ... More
Neutrophil transepithelial migration: evidence for sequential, contact-dependent signaling events and enhanced paracellular permeability independent of transjunctional migration.
AuthorsEdens HA, Levi BP, Jaye DL, Walsh S, Reaves TA, Turner JR, Nusrat A, Parkos CA,
JournalJ Immunol
PubMed ID12077279
Active migration of polymorphonuclear leukocytes (PMN) through the intestinal crypt epithelium is a hallmark of inflammatory bowel disease and correlates with patient symptoms. Previous in vitro studies have shown that PMN transepithelial migration results in increased epithelial permeability. In this study, we modeled PMN transepithelial migration across T84 monolayers and ... More
Mediation of proliferating cell nuclear antigen (PCNA)-dependent DNA replication through a conserved p21(Cip1)-like PCNA-binding motif present in the third subunit of human DNA polymerase delta.
AuthorsDucoux M, Urbach S, Baldacci G, Hübscher U, Koundrioukoff S, Christensen J, Hughes P,
JournalJ Biol Chem
PubMed ID11595739
The subunit that mediates binding of proliferating cell nuclear antigen (PCNA) to human DNA polymerase delta has not been clearly defined. We show that the third subunit of human DNA polymerase delta, p66, interacts with PCNA through a canonical PCNA-binding sequence located in its C terminus. Conversely, p66 interacts with ... More
Hormonal control of reversible translocation of perilipin B to the plasma membrane in primary human adipocytes.
AuthorsAboulaich N, Vener AV, Strålfors P,
JournalJ Biol Chem
PubMed ID16527823
In adipocytes, perilipin coats and protects the central lipid droplet, which stores triacylglycerol. Alternative mRNA splicing gives rise to perilipin A and B. Hormones such as catecholamines and insulin regulate triacylglycerol metabolism through reversible serine phosphorylation of perilipin A. It was recently shown that perilipin was also located in triacylglycerol-synthesizing ... More
Phycobilisome linker proteins are phosphorylated in Synechocystis sp. PCC 6803.
AuthorsPiven I, Ajlani G, Sokolenko A,
JournalJ Biol Chem
PubMed ID15805115
The controversial issue of protein phosphorylation from the photosynthetic apparatus of Synechocystis sp. PCC 6803 has been reinvestigated using new detection tools that include various immunological and in vivo labeling approaches. The set of phosphoproteins detected with these methods includes ferredoxin-NADPH reductase and the linker proteins of the phycobilisome antenna. ... More
Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation.
AuthorsFinigan JH, Dudek SM, Singleton PA, Chiang ET, Jacobson JR, Camp SM, Ye SQ, Garcia JG,
JournalJ Biol Chem
PubMed ID15710622
Increased endothelial cell (EC) permeability is central to the pathophysiology of inflammatory syndromes such as sepsis and acute lung injury (ALI). Activated protein C (APC), a serine protease critically involved in the regulation of coagulation and inflammatory processes, improves sepsis survival through an unknown mechanism. We hypothesized a direct effect ... More
Ubiquitination and proteolysis of cancer-derived Smad4 mutants by SCFSkp2.
AuthorsLiang M, Liang YY, Wrighton K, Ungermannova D, Wang XP, Brunicardi FC, Liu X, Feng XH, Lin X,
JournalMol Cell Biol
PubMed ID15314162
Smad4/DPC4, a common signal transducer in transforming growth factor beta (TGF-beta) signaling, is frequently inactivated in human cancer. Although the ubiquitin-proteasome pathway has been established as one mechanism of inactivating Smad4 in cancer, the specific ubiquitin E3 ligase for ubiquitination-mediated proteolysis of Smad4 cancer mutants remains unclear. In this report, ... More
Cellular response to hypoxia involves signaling via Smad proteins.
AuthorsZhang H, Akman HO, Smith EL, Zhao J, Murphy-Ullrich JE, Batuman OA,
JournalBlood
PubMed ID12411310
The transforming growth factor-beta (TGF-beta) family of cytokines regulates vascular development and inflammatory responses. We have recently shown that exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia (1% O(2)) increases gene expression and bioactivation of TGF-beta2 and induces its downstream effectors, Smad proteins (Smads), to associate with DNA. ... More
Serine phosphorylation of p60 tumor necrosis factor receptor by PKC-delta in TNF-alpha-activated neutrophils.
AuthorsKilpatrick LE, Song YH, Rossi MW, Korchak HM,
JournalAm J Physiol Cell Physiol
PubMed ID11078718
Tumor necrosis factor-alpha (TNF-alpha) triggers degranulation and oxygen radical release in adherent neutrophils. The p60TNF receptor (p60TNFR) is responsible for proinflammatory signaling, and protein kinase C (PKC) is a candidate for the regulation of p60TNFR. Both TNF-alpha and the PKC-activator phorbol 12-myristate 13-acetate triggered phosphorylation of p60TNFR. Receptor phosphorylation was ... More
Bryostatin-1 enhances barrier function in T84 epithelia through PKC-dependent regulation of tight junction proteins.
AuthorsYoo J, Nichols A, Mammen J, Calvo I, Song JC, Worrell RT, Matlin K, Matthews JB,
JournalAm J Physiol Cell Physiol
PubMed ID12660149
Protein kinase C (PKC) is known to regulate epithelial barrier function. However, the effect of specific PKC isozymes, and their mechanism of action, are largely unknown. We determined that the nonphorbol ester PKC agonist bryostatin-1 increased transepithelial electrical resistance (TER), a marker of barrier function, in confluent T84 epithelia. Bryostatin-1, ... More
Regulation of the blood-testis barrier by coxsackievirus and adenovirus receptor.
AuthorsSu L, Mruk DD, Cheng CY,
JournalAm J Physiol Cell Physiol
PubMed ID22875787
The blood-testis barrier (BTB) divides the seminiferous epithelium into the basal and the adluminal compartment. It restricts paracellular diffusion of molecules between Sertoli cells, confers cell polarity, and creates a unique microenvironment in the adluminal compartment for spermatid development. However, it undergoes restructuring during the epithelial cycle so that preleptotene ... More
Mechanical fluctuations of the membrane-skeleton are dependent on F-actin ATPase in human erythrocytes.
AuthorsTuvia S, Levin S, Bitler A, Korenstein R
JournalJ Cell Biol
PubMed ID9647648
Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark field microscopy, were shown to depend, to a large extent, on intracellular MgATP (Levin, S.V., and R. Korenstein. 1991. Biophys. J. 60:733-737). The present study extends that investigation and associates CMF with F-actin's ATPase activity. MgATP was found to ... More
Smad proteins exist as monomers in vivo and undergo homo- and hetero-oligomerization upon activation by serine/threonine kinase receptors.
AuthorsKawabata M, Inoue H, Hanyu A, Imamura T, Miyazono K
JournalEMBO J
PubMed ID9670020
Smad proteins are signal transducers for the members of the transforming growth factor-beta (TGF-beta) superfamily. Here we show that, in the absence TGF-beta stimulation, Smads exist as monomers in vivo. Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGF-beta type I receptor, and this oligomerization does not ... More
Regulation of organelle movement in melanophores by protein kinase A (PKA), protein kinase C (PKC), and protein phosphatase 2A (PP2A).
AuthorsReilein AR, Tint IS, Peunova NI, Enikolopov GN, Gelfand VI
JournalJ Cell Biol
PubMed ID9700167
We used melanophores, cells specialized for regulated organelle transport, to study signaling pathways involved in the regulation of transport. We transfected immortalized Xenopus melanophores with plasmids encoding epitope-tagged inhibitors of protein phosphatases and protein kinases or control plasmids encoding inactive analogues of these inhibitors. Expression of a recombinant inhibitor of ... More
Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex.
AuthorsNunbhakdi-Craig V, Machleidt T, Ogris E, Bellotto D, White CL, Sontag E
JournalJ Cell Biol
PubMed ID12196510
Tight junctions (TJs) play a crucial role in the establishment of cell polarity and regulation of paracellular permeability in epithelia. Here, we show that upon calcium-induced junction biogenesis in Madin-Darby canine kidney cells, ABalphaC, a major protein phosphatase (PP)2A holoenzyme, is recruited to the apical membrane where it interacts with ... More
Protein kinase C? phosphorylates occludin and promotes assembly of epithelial tight junctions.
AuthorsJain S, Suzuki T, Seth A, Samak G, Rao R
JournalBiochem J
PubMed ID21545357
Protein kinases play an important role in the regulation of epithelial tight junctions. In the present study, we investigated the role of PKC? (protein kinase C?) in tight junction regulation in Caco-2 and MDCK (Madin-Darby canine kidney) cell monolayers. Inhibition of PKC? by a specific PKC? pseudosubstrate peptide results in ... More