Differential activation of the extracellular signal-regulated kinase, Jun Kinase and Janus Kinase-Stat pathways by oncostatin M and basic fibroblast growth factor in AIDS-derived Kaposiʼs sarcoma cells

Faris, Mary; Ensoli, Barbara; Stahl, Neil; Yancopouloš, George D.; Nguyen, Andrew; Wang, Schwale; Nel, André E.

doi:10.1097/00002030-199604000-00004

Cited by 38 publications

(24 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, FGF-2-induced cell survival was not affected upon treatment with PP1, and there was only a modest stimulatory effect on Src activity by FGF-2 in these cells. Ligation of the bFGF receptor failed to induce JAK activity in AIDS-derived Kaposi's sarcoma cells (54). In contrast to the above observations, our results indicate that inhibition of JAK-2 or Src attenuates bFGF-stimulated HUVEC proliferation, thus demonstrating the importance of these proteins in the growth of HUVEC mediated by bFGF.…”

Section: Dual Kinase Activation Of Stat-3 By Pafcontrasting

confidence: 93%

Phosphorylation of STAT-3 in Response to Basic Fibroblast Growth Factor Occurs through a Mechanism Involving Platelet-activating Factor, JAK-2, and Src in Human Umbilical Vein Endothelial Cells

Deo¹,

Axelrad²,

Robert³

et al. 2002

Journal of Biological Chemistry

112

View full text Add to dashboard Cite

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid with multiple pathological and physiological effects. We have shown that basic fibroblast growth factor (bFGF) supplementation induces rapid proliferation of human umbilical vein endothelial cells (HUVEC), which is reduced upon removal of bFGF or by bFGF immunoneutralization. The PAF receptor antagonist LAU-8080 inhibited bFGF-stimulated HUVEC proliferation, indicating the involvement of PAF in the bFGF-mediated signaling of HUVEC. Although FGF receptor phosphorylation was not affected by LAU-8080, the bFGF-mediated prolonged phosphorylation, and activation of Erk-1 and -2 were attenuated. Phosphorylation of STAT-3 was observed in the presence of PAF or bFGF, which was attenuated by PAFR antagonists. PAF-induced STAT-3 phosphorylation observed in HUVEC pretreated with either Src inhibitor PP1 or JAK-2 inhibitor AG-490 indicated (i) immediate (1 min) phosphorylation of STAT-3 is dependent on Src, (ii) JAK-2-dependent STAT-3 phosphorylation occurs after the delayed (30 min) PAF exposure, and (iii) prolonged (60 min) STAT-3 phosphorylation may be either through Src and/or JAK-2. Attenuation of the STAT-3 phosphorylation by the PAFR antagonists indicated signaling through the PAF receptor. Taken together, these findings suggest the production of PAF is important for bFGF-mediated signaling and that a dual kinase mechanism is involved in the PAF-mediated signal transduction cascade.is an ether phospholipid second messenger that mediates a number of biological responses, including inflammatory and immune responses, shock, embryogenesis, and cell differentiation (for review, see Ref. 1). PAF is also a potent mediator of pathological angiogenesis associated with tumor expansion and metastasis (2, 3). Hepatocyte growth factor, tumor necrosis factor-␣, and thrombopoietin have been shown to induce angiogenesis through a mechanism involving PAF (4, 5). Many cells produce PAF, including monocytes, endothelial cells, neutrophils, and lymphocytes, and these cell types can themselves become targets of PAF bioactions (6). PAF acts through a specific Gprotein-linked receptor containing seven ␣-helical domains that span the plasma membrane (7) and has been localized to the plasmalemma (8) and a large endosomal compartment on human umbilical vein endothelial cells (HUVEC) (9). PAF also up-regulates the expression of its own receptor in several cell types including human alveolar macrophages (10) and rat epithelial cells (11), thus potentially providing a positive feedback loop for PAF action.Of the 20 members of the FGF family of growth factors, only acidic FGF and basic FGF (bFGF) have been shown to regulate proliferation and migration of capillary endothelial cells (for review, see Refs. 12 and 13). Although bFGF does not contain a traditional signal sequence, it is now clear that it is secreted via a tightly regulated non-conventional secretory pathway and is localized in the basement membrane and extracellular matrix of numerous tissues (14). bFGF binds t...

show abstract

Section: Dual Kinase Activation Of Stat-3 By Pafcontrasting

confidence: 93%

Phosphorylation of STAT-3 in Response to Basic Fibroblast Growth Factor Occurs through a Mechanism Involving Platelet-activating Factor, JAK-2, and Src in Human Umbilical Vein Endothelial Cells

Deo¹,

Axelrad²,

Robert³

et al. 2002

Journal of Biological Chemistry

112

View full text Add to dashboard Cite

show abstract

“…The JAK1/STAT1 signaling pathway is commonly linked to the receptors of the IL-6-related cytokine subfamily (31-34), IFN-␥, or polypeptide growth factor receptors (35)(36)(37)(38), respectively. While members of the IL-6 family such as leukemia inhibitory factor, oncostatin M, and IL-11, as well as the GPI-anchored ciliary neurotrophic factor (CNTF), utilize gp130 as a common signal transducer.…”

Section: Discussionmentioning

confidence: 99%

Urokinase Receptor Is Associated with the Components of the JAK1/STAT1 Signaling Pathway and Leads to Activation of This Pathway upon Receptor Clustering in the Human Kidney Epithelial Tumor Cell Line TCL-598

Koshelnick

Ehart

Hufnagl

et al. 1997

Journal of Biological Chemistry

163

107

View full text Add to dashboard Cite

The urokinase-type plasminogen activator (uPA) binds to cells via a specific receptor attached to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. Despite the lack of a transmembrane domain, the urokinase receptor (uPAR) is capable of transducing extracellular signals affecting growth, migration, and adhesion. Several Tyr kinases of the src family as well as ␤1, ␤2, and ␤3 integrins were found to be associated with the uPAR. We found that in the human kidney epithelial line TCL-598, also components of the JAK1/STAT1 signal transduction pathway including gp130, are associated with uPAR as revealed by coimmunoprecipitation and are co-localized in caveolae. Upon clustering of uPA⅐uPAR complex by a monoclonal antibody, JAK1 associates with uPAR, which in turn leads to STAT1 phosphorylation, dimerization, specific binding to DNA, and gene activation. To prove the dependence of STAT1 activation on the uPAR, TCL-598 cells were treated with sense and antisense uPAR oligonucleotides. In antisense-treated cells in which uPAR expression was reduced to less then one third, activation of STAT1 by the clustering antibody was abolished while STAT1 activation by interferon-␥ was unaffected. Therefore, in this cell line, uPA⅐uPAR also utilizes the JAK1/STAT1 pathway for signaling, and gp130 might be the transmembrane adapter for this signal transduction pathway.The urokinase-type plasminogen activator (uPA) 1 is a serine protease that promotes pericellular proteolysis during cell migration, angiogenesis, wound healing, and tumor invasion (1-5). In addition, binding of uPA to the specific receptor (uPAR) could induce numerous intracellular signaling events. These include serine phosphorylation of cytokeratins (6); tyrosine phosphorylation of a 38-kDa protein (7); association of uPAR with several tyrosine-kinases of the src family (p60 fyn , p53/ p56 lyn , p56/p59 hck

show abstract

“…In contrast to the results of Wijelath et al 33 using bovine aortic endothelial cells, we have not found any induction of bFGF by OSM in HMEC-1s. Mechanisms by which OSM stimulates cell proliferation could be related to the induction of phosphorylation of mitogen-activated protein kinases (MAPKs), since OSM has recently been found to activate the MAPK/ERK kinase on AIDS-derived Kaposi sarcoma cells, 34 or by a specific tyrosine phosphorylation. 35 Binding studies of endothelial cells suggest the presence of a high-affinity receptor for OSM, with an apparent K d of 15 pmol/L, and a low-affinity receptor, with an apparent K d of 1 nmol/L.…”

Section: Vasse Et Almentioning

confidence: 99%

Oncostatin M Induces Angiogenesis In Vitro and In Vivo

Vasse

Pourtau

Trochon

et al. 1999

ATVB

121

101

View full text Add to dashboard Cite

Abstract-Neovascularization of the atherosclerotic plaque is responsible for its weakening and consequently for the complications of vascular disease. Macrophages are a source of growth factors that can modulate angiogenesis. In this study, we analyzed the effect of oncostatin M (OSM) on angiogenesis, as it could be involved in the development of atherosclerosis. The effect of OSM was compared with those of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). On human dermal microvasculature endothelial cells (HMEC-1s), OSM (22.5 to 112.5 pmol/L) induced a dose-dependent increase in cell proliferation greater than that induced by the classic angiogenic factors vascular endothelial growth factor (VEGF; 543 pmol/L) and basic fibroblast growth factor (bFGF; 1.1 nmol/L). LIF (19 to 475 pmol/L) induced only a 30% increase in cell proliferation, and IL-6 had no effect. Furthermore, in a modified Boyden-chamber model, OSM, LIF, and IL-6 were chemoattractant for HMEC-1s. In a tridimensional gel of fibrin, OSM increased tube formation and tube length, which were already noticeable by day 3. LIF and IL-6 induced a weaker effect that was only obvious by day 10. The angiogenic effect of OSM was also demonstrated in vivo in a rabbit corneal model: OSM was more potent than LIF, the length of the neovessels being longer with OSM than with LIF, whereas IL-6 was without effect. We tested factors that could be involved in the proliferative effect of OSM on HMEC-1s. OSM induced only a slight increase in the urokinase receptor and a 60% increase in VEGF secretion, whereas it does not modify IL-8 secretion or bFGF levels. The effect of OSM seems to depend on endothelial cell origin and cell species: OSM (up to 112.5 pmol/L) did not induce human umbilical vein endothelial cell proliferation and even had a small inhibitory effect (17%) on calf pulmonary artery endothelial cells. In conclusion, OSM induces an angiogenic effect on capillary endothelial cells, which could be, at least in part, implicated in pathological processes such as atherosclerosis or tumor growth. Key Words: angiogenesis Ⅲ atherosclerosis Ⅲ oncostatin M Ⅲ leukemia inhibitory factor Ⅲ vascular endothelial growth factor I t is now established that the functional role of the macrophage extends far beyond its originally recognized role as a scavenger cell. Monocytes in particular are recognized as angiogenesis effector cells that produce a number of growth stimulators and inhibitors, proteolytic enzymes, and cytokines that can influence 1 or more steps in the angiogenesis cascade. It has been shown that activated monocytes or their culture supernatants induce new capillary growth in vitro and angiogenesis in vivo. 1,2 However, recent evidence also suggests that capillary regression may be mediated by monocytes by producing antiangiogenic factors in vitro and in vivo. [3][4][5] Thus, macrophages could be involved in both stimulation and suppression of angiogenesis.Because macrophages reside at the sites of atherosclerotic plaques in the vessel wall and because the...

show abstract

Differential activation of the extracellular signal-regulated kinase, Jun Kinase and Janus Kinase-Stat pathways by oncostatin M and basic fibroblast growth factor in AIDS-derived Kaposiʼs sarcoma cells

Cited by 38 publications

References 0 publications

Phosphorylation of STAT-3 in Response to Basic Fibroblast Growth Factor Occurs through a Mechanism Involving Platelet-activating Factor, JAK-2, and Src in Human Umbilical Vein Endothelial Cells

Phosphorylation of STAT-3 in Response to Basic Fibroblast Growth Factor Occurs through a Mechanism Involving Platelet-activating Factor, JAK-2, and Src in Human Umbilical Vein Endothelial Cells

Urokinase Receptor Is Associated with the Components of the JAK1/STAT1 Signaling Pathway and Leads to Activation of This Pathway upon Receptor Clustering in the Human Kidney Epithelial Tumor Cell Line TCL-598

Oncostatin M Induces Angiogenesis In Vitro and In Vivo

Contact Info

Product

Resources

About