检索结果-内蒙古大学图书馆

MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein (SREBP)-1a at serine 117 in vitro

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第43期275卷 33302-33307页

作者： Roth, G Kotzka, J Kremer, L Lehr, S Lohaus, C Meyer, HE Krone, W Müller-Wieland, D Univ Cologne Klin & Poliklin Innere Med Klin 2 D-50924 Cologne Germany Ruhr Univ Bochum Prot Strukturlab D-50924 Cologne Germany

Sterol regulatory element-binding protein (SREBP)-1a is a transcription factor sensing cellular cholesterol levels and integrating gene regulatory signals mediated by MAP kinase cascades, Here we report the identification of serine 117 in SREBP-1a as the major phosphorylation site of the MAP kinases Erk1/2. This site was identified by nanoelectrospray mass spectrometry and peptide sequencing of recombinant fusion proteins phosphorylated by Erk1/2 in vitro. Serine 117 was verified as the major phosphorylation site by in vitro mutagenesis, Mutation of serine 117 to alanine abolished Erk2-mediated phosphorylation in vitro and the MAP kinase-related transcriptional activation of SREBP-1a by insulin and platelet-derived growth factor in vivo. Our data indicate that the MAP kinase-mediated effects on SREBP-1a-regulated target genes are linked to this phosphorylation site.

关键词：氨基酸序列 CCAAT增强子结合蛋白类/化学 CCAAT增强子结合蛋白类/代谢 DNA结合蛋白质类/化学 DNA结合蛋白质类/代谢胰岛素/药理学丝裂原活化蛋白激酶1/生理学丝裂原活化蛋白激酶3 丝裂原激活蛋白激酶类/生理学分子序列数据磷酰化血小板源性生长因子/药理学受体 LDL/遗传学丝氨酸/代谢胆固醇调节元件结合蛋白质1 转录因子人类

来源：评论

学校读者我要写书评

暂无评论

The low M_r protein-tyrosine phosphatase is involved in Rho-mediated cytoskeleton rearrangement after integrin and platelet-derived growth factor stimulation

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第7期275卷 4640-4646页

作者： Chiarugi, P Cirri, P Taddei, L Giannoni, E Camici, G Manao, G Raugei, G Ramponi, G Univ Florence Dipartimento Sci Biochim I-50134 Florence Italy

The low molecular weight protein-tyrosine phosphatase (LMW-PTP) is an enzyme that is involved in the early events of platelet-derived growth factor (PDGF) receptor signal transduction, In fact, LMW-PTP is able to specifically bind and dephosphorylate activated PDGF receptor, thus modulating PDGF-induced mitogenesis. In particular, LMW-PTP is involved in pathways that regulate the transcription of the immediately early genes myc and fos in response to growth factor stimulation. Recently, we have found that LMW-PTP exists constitutively in cytosolic and cytoskeleton-associated localization and that, after PDGF stimulation, c-Src is able to bind and phosphorylate LMW-PTP only in the cytoskeleton-associated fraction. As a consequence of its phosphorylation, LMW-PTP increases its catalytic activity about 20-fold, In this study, our interest was to investigate the role of LMW-PTP phosphorylation in cellular response to PDGF stimulation, To address this issue, we have transfected in NIH-3T3 cells a mutant form of LMW-PTP in which the c-Src phosphorylation sites (Tyr(131) and Tyr(132)) were mutated to alanine, We have established that LMW-PTP phosphorylation by c-Src after PDGF treatment strongly influences both cell adhesion and migration. In addition, we have discovered a new LMW-PTP substrate localized in the cytoskeleton that becomes tyrosine-phosphorylated after PDGF treatment: p190Rho-GAP, Hence, LMW-PTP plays multiple roles in PDGF receptor-mediated mitogenesis, since it can bind and dephosphorylate PDGF receptor, and, at the same time, the cytoskeleton-associated LMW-PTP, through the regulation of the p190Rho-GAP phosphorylation state, controls the cytoskeleton rearrangement in response to PDGF stimulation.

关键词： 3T3细胞细胞黏附/生理学细胞骨架/药物作用细胞骨架/代谢细胞骨架/超微结构 DNA结合蛋白质类 GTP酶激活蛋白质类鸟嘌呤核苷酸交换因子类整合素类/生理学分子量诱变定点核蛋白质类/生理学磷蛋白类/生理学磷酰化血小板源性生长因子/药理学蛋白质酪氨酸磷酸酶类/化学蛋白质酪氨酸磷酸酶类/遗传学蛋白质酪氨酸磷酸酶类/代谢阻遏蛋白质类底物特异性动物小鼠

来源：评论

学校读者我要写书评

暂无评论

Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells

引用

GASTROENTEROLOGY 2000年第2期119卷 479-492页

作者： Failli, P DeFranco, RMS Caligiuri, A Gentilini, A Romanelli, RG Marra, F Batignani, G Guerra, CT Laffi, G Gentilini, P Pinzani, M Univ Florence Dipartimento Med Interna I-50134 Florence Italy Univ Florence Dipartimento Farmacol Preclin & Clin I-50134 Florence Italy Univ Florence Dipartimento Fisiopatol Clin Unita Chirurg I-50134 Florence Italy

Background & Aims: Nitrovasodilators have been proposed for the treatment of portal hypertension alone or in combination with beta-blockers. In addition to their vasodilatory properties, nitric oxide (NO) donors may exert direct antifibrogenic properties. We evaluated the effect of nitroglycerin (NTG) and S-nitroso-N-acetyl penicillamine (SNAP) on the mitogenic and chemotactic properties of platelet-derived growth factor (PDGF)BB and the modulation of the relative intracellular signaling pathways in fully activated human hepatic stellate cells (HSCs), a cell type that plays an active role in liver fibrogenesis and portal hypertension. Methods Br Results: Both NTG and SNAP induced a dose-dependent decrease in PDGF-induced DNA synthesis and cell migration, which was associated with a decrease in PDGF-induced intracellular Ca2+ increase and extracellular signal-regulated kinase (ERK) activity. These effects were not related to activation of the classic soluble guanylate cyclase (sGC)/guanosine 3',5'-cyclic monophosphate pathway;accordingly, Western blot analysis of HSC lysates revealed the absence of the alpha(1)beta(1) ubiquitous subunits of sGC, whereas they were detectable in quiescent HSCs, freshly isolated from normal human liver. Conversely, both NTG and SNAP induced a more than 10-20-fold increase in prostaglandin E-2 in cell supernatants within 1 minute, associated with an increase in intracellular adenosine 3',5'-cyclic monophosphate levels. Accordingly, the inhibitory effects of NO donors on PDGF action and signaling were eliminated after preincubation with ibuprofen, Conclusions: These results suggest that NO donors may exert a direct antifibrogenic action by inhibiting proliferation, motility, and contractility of HSCs in addition to a reduction of fibrillar extracellular matrix accumulation.

关键词：钙/代谢细胞分裂/药物作用细胞运动/药物作用细胞培养的趋化作用/药物作用环GMP/代谢地诺前列酮/代谢鸟苷酸环化酶/代谢止血药/药理学肝/细胞学肝/酶学一氧化氮供体/药理学硝酸甘油/药理学青霉胺/类似物和衍生物青霉胺/药理学血小板源性生长因子/药理学信号传导/药物作用凝血酶/药理学 C型磷脂酶类/代谢血管舒张药/药理学人类

来源：评论

学校读者我要写书评

暂无评论

Cross-talk between phosphatidylinositol 3-kinase and sphingomyelinase pathways as a mechanism for cell survival/death decisions

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第13期275卷 9628-9635页

作者： Burow, ME Weldon, CB Collins-Burow, BM Ramsey, N McKee, A Klippel, A McLachlan, JA Clejan, S Beckman, BS Tulane Univ Med Ctr Dept PharmacolSch Med Tulane Ctr Bioenvironm Res New Orleans LA 70112 USA Tulane Univ Sch Med Dept Pathol & Lab Med New Orleans LA 70112 USA Tulane Univ Sch Med Dept Surg New Orleans LA 70112 USA Tulane Univ Sch Med Tulane Canc Ctr New Orleans LA 70112 USA Tulane Univ Sch Med Dept Pharmacol New Orleans LA 70112 USA Tulane Univ Sch Med Mol & Cellular Biol Program New Orleans LA 70112 USA Chiron Corp Emeryville CA 94608 USA

Peptide hormones act to regulate apoptosis through activation of multiple pro- and anti-apoptotic signaling cascades of which lipid signaling events represent an important facet of the cellular rheostat that determines survival and death decisions. Activation of sphingomyelinase, which generates ceramide, is an intermediate in cellular stress responses and induction of apoptosis in many systems. Conversely, phosphatidylinositol 3-kinase (PI3K) is a critical signaling molecule involved in regulating cell survival and proliferation pathways. In the present study, we investigate cross-talk between the PI3K and sphingomyelinase pathways as a mechanism for regulation of cell survival/death decisions. We show that phorbol ester, insulin-like growth factor 1, and a constitutively active PI3K suppress both tumor necrosis factor-induced apoptosis and ceramide generation. Conversely, inhibition of the PI3K pathway with expression of a kinase-dead PI3K both prevented survival signaling and enhanced tumor necrosis factor-induced ceramide generation. The ability of exogenous sphingomyelinase to induce ceramide generation was partially suppressed by expression of constitutively active PI3K and enhanced by inhibition of PI3K suggesting that cross-talk between PI3K and ceramide generation within cells is regulated subsequent to activation of sphingomyelinase.

关键词：细胞凋亡/生理学细胞存活/生理学神经酰胺类/拮抗剂和抑制剂神经酰胺类/生理学酶激活成纤维细胞生长因子/药理学磷酸肌醇3-激酶类/代谢血小板源性生长因子/药理学信号传导鞘磷脂磷酸二酯酶/代谢十四酰佛波乙酯/药理学肿瘤细胞培养的肿瘤坏死因子α/生理学人类

来源：评论

学校读者我要写书评

暂无评论

Activation of mitogen-activated protein kinase pathways by cyclic GMP and cyclic GMP-dependent protein kinase in contractile vascular smooth muscle cells

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第48期274卷 34301-34309页

作者： Komalavilas, P Shah, PK Jo, HJ Lincoln, TM Univ Alabama Birmingham Div Mol & Cellular Pathol Dept Pathol Birmingham AL 35294 USA

Vascular smooth muscle cells (VSMC) exist in either a contractile or a synthetic phenotype in vitro and in vivo. The molecular mechanisms regulating phenotypic modulation are unknown. Previous studies have suggested that the serine/threonine protein kinase mediator of nitric oxide (NO) and cyclic GMP (cGMP) signaling, the cGMP-dependent protein kinase (PKG) promotes modulation to the contractile phenotype in cultured rat aortic smooth muscle cells (RASMC). Because of the potential importance of the mitogen-activated protein kinase (MAP kinase) pathways in VSMC proliferation and phenotypic modulation, the effects of PKG expression in PKG-deficient and PKG-expressing adult RASMC on MAP kinases were examined. In PKG-expressing adult RASMC, 8-para-chlorophenylthio-cGMP activated extracellular signal- regulated kinases (ERK1/2) and c-Jun N-terminal kinase (JNK). The major effect of PKG activation was increased activation by MAP kinase kinase (MEK). The cAMP analog, 8-Br-cAMP inhibited ERK1/2 activation in PKG-deficient and PKG-expressing RASMC but had no effect on JNK activity. The effects of PKG on ERK and JNK activity were additive with those of platelet-derived growth factor (PDGF), suggesting that PKG activates MEK through a pathway not used by PDGF. The stimulatory effects of cGMP on ERK and JNK activation mere also observed in low-passaged, contractile RASMC still expressing endogenous PKG, suggesting that the effects of PKG expression were not artifacts of cell transfections. These results suggest that in contractile adult RASMC, NO-cGMP signaling increases MAP kinase activity. Increased activation of these MAP kinase pathways may be one mechanism by which cGMP and PKG activation mediate c-fos induction and increased proliferation of contractile adult RASMC.

关键词： 8-溴环腺苷一磷酸/药理学生物碱类/药理学主动脉卡唑类细胞培养的环GMP/类似物和衍生物环GMP/药理学环GMP依赖性蛋白激酶类/拮抗剂和抑制剂环GMP依赖性蛋白激酶类/遗传学环GMP依赖性蛋白激酶类/代谢酶激活/药物作用酶抑制剂/药理学基因表达吲哚类/药理学 JNK丝裂原活化蛋白激酶类 MAP激酶激酶4 MAP激酶激酶激酶类/代谢丝裂原活化蛋白激酶1/代谢丝裂原活化蛋白激酶3 丝裂原激活蛋白激酶激酶类/代谢丝裂原激活蛋白激酶类/代谢肌收缩/药物作用肌收缩/生理学肌平滑血管/细胞学肌平滑血管/药物作用肌平滑血管/酶学血小板源性生长因子/药理学蛋白质丝氨酸苏氨酸激酶吡咯类/药理学大鼠 Sprague-Dawley 重组融合蛋白质类/药物作用重组融合蛋白质类/遗传学重组融合蛋白质类/代谢硫代核苷酸类/药理学时间因素转染肿瘤坏死因子α/药理学 p38丝裂原活化蛋白激酶类动物大鼠

来源：评论

学校读者我要写书评

暂无评论

Vinexin forms a signaling complex with Sos and modulates epidermal growth factor-induced c-Jun N-terminal kinase/stress-activated protein kinase activities

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第50期274卷 35933-35937页

作者： Akamatsu, M Aota, S Suwa, A Ueda, K Amachi, T Yamada, KM Akiyama, SK Kioka, N Kyoto Univ Grad Sch Agr Div Appl Life Sci Sakyo Ku Kyoto 6068502 Japan Biomol Engn Res Inst Suita Osaka 565 Japan NIDCR Craniofacial Dev Biol & Regenerat Branch NIH Bethesda MD 20892 USA NIEHS Mol Carcinogenesis Lab NIH Res Triangle Pk NC 27709 USA

Vinexin, a novel protein that plays a hey role in cell spreading and cytoskeletal organization, contains three SH3 domains and binds to vinculin through its first and second SH3 domains. We show here that the third SH3 domain binds to Sos, a guanine nucleotide exchange factor for Pas and Pac, both in vitro and in vivo. Point mutations in the third SH3 domain abolished the vinexin-Sos interaction. Stimulation of NIH/3T3 cells with serum, epidermal growth factor (EGF), or platelet derived growth factor (PDGF) decreased the electro phoretic mobility of Sos and concomitantly inhibited formation of the vinexin-Sos complex. Phosphatase treatment of lysates restored the binding of Sos to vinexin, suggesting that signaling from serum, EGF, or PDGF regulates the vinexin-Sos complex through the Sos phosphorylation. To evaluate the function of vinexin downstream of growth factors, we examined the effects of wild-type and mutant vinexin expression on extracellular signal-regulated kinase (Erk) and c-Jun N-terminal kinase/stress activated protein kinase (JNK/SAPK) activation in response to EGF. Exogenous expression of vinexin beta in NIH/3T3 cells enhanced JNK/SAPK activation but did not affect Erk activation. Moreover mutations in the third SH3 domain abolished EGF activation of JNK/SAPK in a dominant-negative fashion, whereas they slightly stimulated Erk. Together these results suggest that vinexin can selectively modulate EGF-induced signal transduction pathways leading to JNK/SAPK kinase activation.

关键词： 3T3细胞色谱法亲和表皮生长因子/药理学 JNK丝裂原活化蛋白激酶类动力学丝裂原激活蛋白激酶类/代谢肌蛋白质类/化学肌蛋白质类/分离和提纯肌蛋白质类/代谢磷酰化血小板源性生长因子/药理学点突变重组融合蛋白质类/代谢信号传导 SOS蛋白质类/化学 SOS蛋白质类/分离和提纯 SOS蛋白质类/代谢转染 src同源域动物小鼠

来源：评论

学校读者我要写书评

暂无评论

Bombesin and platelet-derived growth factor induce association of endogenous focal adhesion kinase with Src in intact Swiss 3T3 cells

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第40期274卷 28371-28378页

作者： Salazar, EP Rozengurt, E Univ Calif Los Angeles Sch Med Dept Med Los Angeles CA 90095 USA Univ Calif Los Angeles Inst Mol Biol Los Angeles CA 90095 USA

Stimulation of quiescent Swiss 3T3 cells with bombesin induces a rapid increase in the formation of complexes between focal adhesion kinase (FAK) and Src family members, which can be extracted with a buffer containing Triton, deoxycholate, and SDS but not with a buffer containing Triton alone. An increase in complex formation between FAK and Src in response to bombesin could be detected within 1 min, reached a maximum after 10 min, and declined toward base-line levels after 60 min of bombesin treatment. Bradykinin, endothelin, and lysophosphatidic acid also stimulated FAK-Src complex formation. Bombesin stimulated FAW/Src association through a Ca2+ and phosphatidylinositol 3'-kinase-independent pathway that requires the integrity of the actin filament network and is partly dependent on functional protein kinase C. Treatment with the selective Src kinase inhibitor PP-2 inhibited both FAK activation and phosphorylation of FAK at Tyr(577) induced by bombesin in intact cells. Platelet-derived growth factor at low concentrations (1-10 ng/ml) also induced FAK-Src complex formation via a pathway that depended on the integrity of the actin cytoskeleton and phosphatidylinositol 3'-kinase. Thus, G protein-coupled receptor agonists and platelet-derived growth factor promote complex formation between endogenous FAK and Src in attached cells through different signal transduction pathways.

关键词： 3T3细胞肌动蛋白类/代谢铃蟾肽/药理学钙/代谢细胞黏附分子/代谢细胞骨架/代谢黏着斑激酶1 黏着斑蛋白酪氨酸激酶类癌基因蛋白质pp60(v-src)/代谢磷酸肌醇3-激酶类/代谢血小板源性生长因子/药理学蛋白质结合蛋白激酶C/代谢蛋白酪氨酸激酶类/代谢动物小鼠

来源：评论

学校读者我要写书评

暂无评论

Hydrogen peroxide activates p70^S6k signaling pathway

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第46期274卷 32596-32602页

作者： Bae, GU Seo, DW Kwon, HK Lee, HY Hong, S Lee, ZW Ha, KS Lee, HW Han, JW Sungkyunkwan Univ Coll Pharm Dept Biochem Suwon 440746 South Korea Sungkyunkwan Univ Coll Life Sci & Nat Resources Dept Genet Engn Suwon 440746 South Korea Konyang Univ Coll Med Dept Pharmacol Nonsan 320711 South Korea Korea Basic Sci Inst Biomol Res Grp Taejon 305333 South Korea

We investigated a possible role of reactive oxygen species (ROS) in p70(S6k) activation, which plays an important role in the progression of cells from G(0)/G(1) to S phase of the cell cycle by translational up-regulation of a family of mRNA transcripts that encode for components of the protein synthetic machinery. Treatment of mouse epidermal cell JB6 with H2O2 generated extracellularly by glucose/glucose oxidase led to the activation of p70(S6k) and p90(Rsk) and to phosphorylation of p42(MAPK)/p44(MAPK) The activation of p70(S6k) and p90(Rsk) was dose-dependent and transient, maximal activities being in extracts treated for 15 and 30 min, respectively. Further characterization of ROS-induced activation of p70S6k using specific inhibitors for p70S6k Signaling pathway, rapamycin, and wortmannin revealed that ROS acted upstream of the rapamycin-sensitive component FRAP/RAFT and wortmannin-sensitive component phosphatidylinositol 3-kinase, because both inhibitors caused the inhibition of ROS-induced p70(S6k) activity. In addition, Ca2+ chelation also inhibited ROS-induced activation of p70S6k, indicating that Ca2+ is a mediator of p70(S6k) activation by ROS. However, down-regulation of 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive protein kinase C (PKC) by chronic pretreatment with TPA or a specific PHC inhibitor Re-31-8220 did not block the activation of p70S6k by ROS, indicating that the activation of TPA-responsive PHC was not required for stimulation of p70(S6k) activity by H2O2 in JB6 cells. Exposure of JB6 cells to platelet-derived growth factor or epidermal growth factor led to a rapid increase in H2O2, phosphorylation, and activation of p70(S6k), which were antagonized by the pretreatment of catalase. Taken together, the results suggest that ROS act as a messenger in growth factor-induced p70(S6k) signaling pathway.

关键词：雄二烯类/药理学钙/代谢过氧化氢酶/药理学细胞系酶激活表皮生长因子/药理学基因表达调控酶学/药物作用过氧化氢/药理学吲哚类/药理学小鼠近交BALBC 丝裂原激活蛋白激酶类/代谢磷酰化血小板源性生长因子/药理学蛋白激酶C/拮抗剂和抑制剂活性氧/代谢核糖体蛋白质S6激酶类/遗传学核糖体蛋白质S6激酶类/代谢信号传导/药物作用西罗莫司/药理学十四酰佛波乙酯/药理学动物小鼠

来源：评论

学校读者我要写书评

暂无评论

Altered sensitivity to single-strand-specific reagents associated with the genomic vascular smooth muscle α-actin promoter during myofibroblast differentiation

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第20期275卷 15384-15391页

作者： Becker, NA Kelm, RJ Vrana, JA Getz, MJ Maher, LJ Mayo Clin & Mayo Fdn Dept Biochem & Mol Biol Rochester MN 55905 USA

Stimulation of quiescent AKR-2B mouse fibroblasts with transforming growth factor beta 1 results in uniform conversion to a myofibroblast-like phenotype as judged by a rapid accumulation of smooth muscle alpha-actin mRNA and protein. Because transcriptional regulation of the smooth muscle alpha-actin gene in these cells might be mediated by single-stranded DNA-binding proteins, we have examined the sensitivity of genomic DNA to chemical reagents with specificity for unpaired bases in a region of the promoter previously implicated in Pur alpha, Pur beta, and MSY1 binding in vitro (Kelm, R. J., Jr., Cogan, J. G., Elder, P. K., Strauch, A. R., and Getz, M. J. (1999) J, Biol. Chem. 274, 14238-14245), Our data reveal specific differences between purified DNA treated in vitro and nucleoprotein complexes treated in living cells. Although some differences were observed in quiescent cells, treatment with transforming growth factor beta 1 resulted in the development of additional sensitivity within 1 h. This enhancement was most pronounced in bases immediately upstream of an MCAT enhancer element-containing polypurine-polypyrimidine tract. A TATA-proximal element of similar base distribution showed no such hyperreactivities, These results suggest that activation of the endogenous smooth muscle alpha-actin gene during myofibroblast conversion is accompanied by specific structural changes in the promoter that are consistent with a decline in single-stranded DNA repressor protein binding.

关键词：肌动蛋白类/遗传学碱基序列细胞分化/药物作用 DNA 单链/药物作用增强子元件(遗传学) 表皮生长因子/药理学成纤维细胞/细胞学成纤维细胞/药物作用成纤维细胞/代谢胰岛素/药理学动力学分子序列数据肌平滑血管/代谢血小板源性生长因子/药理学启动区(遗传学) TATA盒转化生长因子β/药理学动物小鼠

来源：评论

学校读者我要写书评

暂无评论

The role of platelet α-granular proteins in the regulation of thrombopoietin messenger RNA expression in human bone marrow stromal cells

引用

BLOOD 2000年第10期95卷 3094-3101页

作者： Sungaran, R Chisholm, OT Markovic, B Khachigian, LM Tanaka, Y Chong, BH Prince Wales Hosp Dept Haematol Randwick NSW 2031 Australia Univ New S Wales Sch Safety Sci Chem Safety & Appl Toxicol Labs Ctr Thrombosis & Vasc Res Kensington NSW 2033 Australia Kirin Brewery Co Ltd Tokyo Japan

Thrombopoietin (TPO), the specific cytokine that regulates platelet production, is expressed in human bone marrow (BM), kidney, and liver. There appears to be no regulation of TPO in the kidney and liver, but TPO messenger RNA (mRNA) expression can be modulated in the stromal cells of the BM. In this study, we used primary human BM stromal cells as a model to study the regulation of TPO mRNA expression in response to various platelet alpha-granular proteins. We showed that platelet-derived growth factor (PDGF) BE and fibroblast growth factor (FGF) 2 stimulated TPO mRNA expression in both a dose-dependent and time-dependent manner. The addition of 50 ng/mL of PDGF and 20 ng/mL of FGF resulted in maximal induction of TPO mRNA expression in 4 hours. We also found that platelet factor 4 (PF4), thrombospondin (TSP), and transforming growth factor-beta (TGF-beta) are negative modulators of megakaryocytopoiesis. We observed suppression in TPO mRNA expression with 1 mu g/mL of both PF4 and TSP and 50 ng/mL of TGF-beta, with maximal suppression occurring 4 hours after the addition of these proteins. Finally, the addition of whole-platelet lysate produced a dose-dependent inhibition of TPO expression. On the basis of these findings, we propose that the platelet alpha-granular proteins studied may regulate TPO gene expression in BM stromal cells by means of a feedback mechanism. (C) 2000 by The American Society of Hematology.

关键词：骨髓/生理学细胞培养的剂量效应关系药物反馈成纤维细胞生长因子2/药理学基因表达调控/药物作用血小板源性生长因子/药理学 RNA 信使/生物合成 RNA 信使/遗传学间质细胞/生理学血小板生成素/生物合成血小板生成素/遗传学人类

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：