scholarly journals Angiotensin II type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase

1997 ◽  
Vol 325 (2) ◽  
pp. 449-454 ◽  
Author(s):  
Katarina BEDECS ◽  
Nathalie ELBAZ ◽  
Malène SUTREN ◽  
Maryline MASSON ◽  
Christiane SUSINI ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Protein Kinase ◽  
Map Kinases ◽  
Tyrosine Phosphatase ◽  
At2 Receptor ◽  
Ang Ii ◽  
Mitogen Activated Protein ◽  
At2 Receptors

Angiotensin II type 2 (AT2) receptors are involved in the inhibition of cell proliferation as well as in apoptosis and neuronal differentiation, through intracellular signalling pathways that remain poorly defined. The present study examines the effect of AT2-receptor stimulation on growth-factor-induced pathways leading to the activation of mitogen-activated protein (MAP) kinases. In N1E-115 neuroblastoma cells, AT2 receptors inhibit the activity of MAP kinases induced by serum as well as by epidermal growth factor. The inhibitory effect of angiotensin II (Ang II) is rapid and transient, and affects both ERK1 and ERK2 (extracellular signal-related protein kinase) isoforms of the enzyme. AT2-mediated MAP kinase inactivation is not sensitive to pertussis toxin or okadaic acid, but involves a vanadate-sensitive protein tyrosine phosphatase (PTP). Expression of MAP kinase phosphatase-1 (MKP-1) is not significantly modified upon AT2-receptor activation, and insensitivity to actinomycin D also rules out transcriptional induction of other MKPs as a possible mechanism for AT2-mediated inactivation of MAP kinases. In addition, we report here that both in N1E-115 cells and in Chinese hamster ovary cells expressing recombinant human AT2 receptors, Ang II rapidly stimulates the catalytic activity of SHP-1, a soluble PTP that has been implicated in termination of signalling by cytokine and growth-factor receptors. These findings thus demonstrate functional negative cross-talk between heptahelical AT2 receptors and receptor tyrosine kinases, and suggest that SHP-1 tyrosine phosphatase is an early transducer of the AT2 receptor signalling pathway.

Upregulation of angiotensin II type 2 receptor expression in estrogen-induced pituitary hyperplasia

2004 ◽  
Vol 286 (5) ◽  
pp. E786-E794 ◽  
Author(s):  
Cecilia Suarez ◽  
Graciela Díaz-Torga ◽  
Arturo González-Iglesias ◽  
Carolina Cristina ◽  
Damasia Becu-Villalobos
Keyword(s):  
Angiotensin Ii ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
At2 Receptor ◽  
Ang Ii ◽  
Pituitary Hyperplasia ◽  
Releasing Effect ◽  
At2 Receptors

Recent evidence shows that reexpression and upregulation of angiotensin II (ANG II) type 2 (AT2) receptor in adult tissues occur during pathological conditions such as tissue hyperplasia, inflammation, and remodeling. In particular, expression of functional AT2 receptors in the pituitary and their physiological significance and regulation have not been described. In this study, we demonstrate that chronic in vivo estrogen treatment, which induces pituitary hyperplasia, enhances local AT2 expression (measured by Western blot and RT-PCR) concomitantly with downregulation of ANG II type 1 (AT1) receptors. In vivo progesterone treatment of estrogen-induced pituitary hyperplasia did not modify either the ANG II receptor subtype expression pattern or octapeptide-induced and AT1-mediated calcium signaling. Nevertheless, an unexpected potentiation of the ANG II prolactin-releasing effect was observed in this group, and this response was sensitive to both AT1 and AT2 receptor antagonists. These data are the first to document that ANG II can act at the pituitary level through the AT2 receptor subtype and that estrogens display a differential regulation of AT1 and AT2 receptors at this level.

scholarly journals Involvement of Protein Kinase Cα (PKCα) in the Early Action of Angiotensin II Type 2 (AT2) Effects on Neurite Outgrowth in NG108–15 Cells: AT2-Receptor Inhibits PKCα and p21ras Activity

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4263-4272 ◽  
Author(s):  
Hélène Beaudry ◽  
Louis Gendron ◽  
Marie-Odile Guimond ◽  
Marcel D. Payet ◽  
Nicole Gallo-Payet
Keyword(s):  
Angiotensin Ii ◽  
Protein Kinase ◽  
Neurite Outgrowth ◽  
At2 Receptor ◽  
Early Action ◽  
Protein Kinase Cα

Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases

2007 ◽  
Vol 293 (4) ◽  
pp. H2403-H2408 ◽  
Author(s):  
Guo-Xing Zhang ◽  
Yukiko Nagai ◽  
Toshitaka Nakagawa ◽  
Hiroshi Miyanaka ◽  
Yoshihide Fujisawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Map Kinase ◽  
Map Kinases ◽  
No Synthase ◽  
Dependent Manner ◽  
Ang Ii ◽  
No Donor ◽  
Mitogen Activated Protein ◽  
Kinase Phosphorylation

Angiotensin II (ANG II) is a powerful activator of mitogen-activated protein (MAP) kinase cascades in cardiovascular tissues through a redox-sensitive mechanism. Nitric oxide (NO) is considered to antagonize the vasoconstrictive and proarteriosclerotic actions of ANG II. However, the role of endogenous NO in ANG II-induced redox-sensitive signal transduction is not yet clear. In this study using catheterized, conscious rats, we found that acute intravenous administration of NG-nitro-l-arginine methyl ester (l-NAME; 5 mg/kg) enhanced phosphorylation of aortic MAP kinases extracellular signal regulated kinase (ERK) 1/2 and p38, which were suppressed only partially by a superoxide dismutase mimetic (Tempol), whereas ANG II-induced MAP kinase phosphorylation was markedly suppressed by Tempol. FK409, a NO donor, had little effect on vascular MAP kinase phosphorylation. On the other hand, acute exposure to a vasoconstrictor dose of ANG II (200 ng·kg−1·min−1 iv) failed to enhance phosphorylation of aortic MAP kinases in the chronically l-NAME-treated rats, whereas the vasoconstrictor effect of ANG II was not affected by l-NAME treatment. Furthermore, three different inhibitors of NO synthase suppressed, in a dose-dependent manner, ANG II-induced MAP kinase phosphorylation in rat vascular smooth muscle cells, which was closely linked to superoxide generation in cells. These results indicate the involvement of endogenous NO synthase in ANG II-induced signaling pathways, leading to activation of MAP kinase, and that NO may have dual effects on the vascular MAP kinase activation associated with redox sensitivity.

scholarly journals Regulation of Vascular Proteoglycan Synthesis by Angiotensin II Type 1 and Type 2 Receptors

2001 ◽  
Vol 12 (12) ◽  
pp. 2609-2615
Author(s):  
Ryoko Shimizu-Hirota ◽  
Hiroyuki Sasamura ◽  
Mizuo Mifune ◽  
Hideaki Nakaya ◽  
Mari Kuroda ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Proteoglycan Synthesis ◽  
At2 Receptor ◽  
Receptor Stimulation ◽  
Epidermal Growth

ABSTRACT. Recent studies have shown that proteoglycans play an important role in the development of vascular disease and renal failure. In this study, the effects of angiotensin II (AngII) type 1 (AT1) and type 2 (AT2) receptor stimulation on glycosaminoglycan and proteoglycan core protein synthesis in vascular smooth muscle cells (VSMC) were examined. Treatment of AT1 receptor-expressing VSMC with AngII resulted in a dose-dependent and time-dependent increase (2- to 4-fold) in 3H-glucosamine/35S-sulfate incorporation, which was abolished by pretreatment with the AT1 receptor antagonist, losartan. The effects of AngII were inhibited by the epidermal growth factor receptor inhibitor, AG1478, and the mitagen-activated protein kinase kinase inhibitor, PD98059, but not the protein kinase C inhibitors, chelerythrine and staurosporine. AngII treatment also resulted in significant increases in the mRNA of the core proteins, versican, biglycan, and perlecan. The effects of AT2 receptor stimulation were examined by retroviral transfection of VSMC with the AT2 receptor. Stimulation of the AT2 receptor in these VSMC-AT2 cells resulted in a significant (1.3-fold) increase in proteoglycan synthesis, which was abolished by the AT2 receptor antagonist, PD123319, and attenuated by pretreatment with pertussis toxin. These results implicate both AT1 and AT2 receptors in the regulation of proteoglycan synthesis and suggest the involvement of epidermal growth factor receptor-dependent tyrosine kinase pathways and Gαi/o-mediated mechanisms in the effects of the two receptors.

Expression of angiotensin II AT2 receptor mRNA during development of rat kidney and adrenal gland

1995 ◽  
Vol 268 (5) ◽  
pp. F922-F930 ◽  
Author(s):  
S. Shanmugam ◽  
C. Llorens-Cortes ◽  
E. Clauser ◽  
P. Corvol ◽  
J. M. Gasc
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Adrenal Gland ◽  
Rat Kidney ◽  
At2 Receptor ◽  
Fetal Life ◽  
Ang Ii ◽  
Receptor Mrna ◽  
Nephron Development

The angiotensin II (ANG II) receptors have been pharmacologically classified into two major distinct types, designated AT1 and AT2. A high transient expression of AT2 receptors in the fetal tissues has been previously demonstrated. This study describes the cellular distribution of AT2 receptor mRNA in the developing rat kidney and adrenal gland by in situ hybridization with 35S-labeled cRNA probes. From day 12 of fetal life (F12) to day 15 postpartum (D15) AT2 mRNA was detected in the undifferentiated nephrogenic mesenchymal tissue but not in the immature and mature glomeruli and tubules of the kidney. No AT2 mRNA was observed in the kidney after D22. The adrenal gland also expressed AT2 receptor mRNA early during development from F12 but, unlike the kidney, continuously expressed the mRNA at high levels through to adulthood. The disappearance of AT2 mRNA in the kidney was synchronous with the completion of nephrogenesis and suggests that ANG II might act through this receptor as a differentiation/growth factor during nephron development. In the adrenal gland ANG II could act as a hormone and also as a differentiation/growth factor via the AT2 receptor.

Regulation of vascular angiotensin II receptors by EGF

1997 ◽  
Vol 273 (4) ◽  
pp. C1241-C1249 ◽  
Author(s):  
Michael E. Ullian ◽  
John R. Raymond ◽  
Mark C. Willingham ◽  
Richard V. Paul
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Protein Kinase ◽  
Pertussis Toxin ◽  
Receptor Expression ◽  
Ang Ii ◽  
Receptor Density ◽  
Kinase C ◽  
Surface Receptor

After vascular endothelial injury, angiotensin II (ANG II) plays a role in the resulting hypertrophic response, and expression of epidermal growth factor (EGF) is enhanced. Therefore, we tested the possibility that EGF regulates vascular ANG II action and receptor expression. Incubation of cultured aortic vascular smooth muscle cells (VSMC) with EGF (or basic fibroblast growth factor but not platelet-derived growth factor isoforms) resulted in concentration-dependent (1–50 ng/ml EGF), time-dependent (>8 h), and reversible decreases in ANG II surface receptor density. For example, a 50% reduction was observed after exposure to 50 ng/ml EGF for 24 h. Incubation of cultured VSMC with 50 ng/ml EGF for 24 h resulted in a 77% reduction in ANG II-stimulated inositol phosphate formation. EGF not only prevented but also reversed ANG II receptor upregulation by 100 nM corticosterone. The specific tyrosine kinase inhibitor tyrphostin A48 (50 μM) reduced EGF-stimulated thymidine incorporation and EGF-stimulated phosphorylation of mitogen-activated protein kinase but did not prevent EGF from reducing ANG II receptor density. Neither pertussis toxin (100 ng/ml) nor downregulation of protein kinase C by phorbol myristate acetate (100 nM for 24 h) prevented EGF from reducing ANG II receptor density. In summary, EGF is a potent negative regulator of vascular ANG II surface receptor density and ANG II action by mechanisms that do not appear to include tyrosine phorphorylation, pertussis toxin-sensitive G proteins, or phorbol ester-sensitive protein kinase C. The possibility that EGF shifts the cell culture phenotype to one that exhibits reduced surface ANG II density cannot be eliminated by the present studies.

scholarly journals Role of Tyrosine Kinase Receptors in Angiotensin II AT2 Receptor Signaling: Involvement in Neurite Outgrowth and in p42/p44mapk Activation in NG108-15 Cells

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4646-4654 ◽  
Author(s):  
Bianca Plouffe ◽  
Marie-Odile Guimond ◽  
Hélène Beaudry ◽  
Nicole Gallo-Payet
Keyword(s):  
Growth Factors ◽  
Nerve Growth Factor ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
At2 Receptor ◽  
Ang Ii ◽  
Nerve Growth

NG108–15 cells, which have a rounding-up morphology when cultured in serum-supplemented medium, extend neurites when stimulated for 3 d with angiotensin II (Ang II). The aim of the present study was to investigate whether growth factor receptors are necessary for mediating the effects of Ang II. A 3-d treatment with AG879, an inhibitor of nerve growth factor receptor TrkA, strongly affected neurite outgrowth and phosphorylation of p42/p44mapk induced by Ang II. PD168393, an inhibitor of epidermal growth factor (EGF) receptor slightly decreased Ang II-induced neurite outgrowth, whereas AG213, an inhibitor of both platelet-derived growth factor receptor and EGF receptor, stimulated neurite outgrowth and p42/p44mapk phosphorylation on its own, without affecting further stimulation with Ang II. Moreover, Ang II induced the phosphorylation of TrkA (maximum at 5 min of incubation in the presence of serum or at 20 min in cells depleted in serum for 2 h) and a rapid increase in Rap1 activity, both effects abolished in cells preincubated with 10 μm AG879. In summary, the present results demonstrate that AT2 receptor-induced sustained activation of p42/p44mapk and corresponding neurite outgrowth are mediated by phosphorylation of the nerve growth factor TrkA receptor. However, the results also point out that the presence of other growth factors, such as EGF or PDFG, may interfere with the effect of Ang II. Altogether, the current findings clearly indicate that the effects of the AT2 receptor on neurite outgrowth dynamics are modulated by the presence of growth factors in the culture medium.

scholarly journals Angiotensin II Activates Mitogen-Activated Protein Kinase Via Protein Kinase C and Ras/Raf-1 Kinase in Bovine Adrenal Glomerulosa Cells

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 1801-1809 ◽  
Author(s):  
Ying Tian ◽  
Roger D. Smith ◽  
Tamas Balla ◽  
Kevin J. Catt
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Time Course ◽  
Mitogen Activated Protein Kinase ◽  
Ang Ii ◽  
Mapk Activation ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Glomerulosa Cells

Abstract Angiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal glomerulosa cells, but little is known about the signaling pathways that mediate these responses. An analysis of the growth-promoting pathways in cultured bovine adrenal glomerulosa cells revealed that Ang II, acting via the AT1 receptor, caused rapid but transient activation of mitogen-activated protein kinase (MAPK), with an ED50 of 10–50 pm. Although neither Ca2+ influx nor Ca2+ release from intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a permissive role in this response. A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded. Ang II also induced the rapid activation of ras and raf-1 kinase with time-courses that correlated with that of MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was sufficient to activate both MAPK and raf-1 kinase. However, whereas PKC depletion had no effect on Ang II-induced raf-1 kinase activation, it attenuated Ang II-induced MAPK activation. Ang II also stimulated a mobility shift of raf-1, reflecting hyperphosphorylation of the kinase. However, unlike its activation, raf-1 hyperphosphorylation was dependent on PKC and its time-course correlated not with activation, but rather with deactivation of the kinase. Taken together, these findings indicate that Ang II stimulates multiple pathways to MAPK activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells.

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