Rapid Transactivation of the Vascular Endothelial Growth Factor Receptor KDR/Flk-1 by the Bradykinin B2 Receptor Contributes to Endothelial Nitric-oxide Synthase Activation in Cardiac Capillary Endothelial Cells

Thüringer, Dominique; Maulon, Laurence; Frelin, Christian

doi:10.1074/jbc.m109493200

Cited by 116 publications

(108 citation statements)

References 47 publications

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“…The apparent discrepancy between our and previous findings may indeed reflect interspecies differences, i.e., VEGF would not have the same effects on rat and human lung cells. Nevertheless, that human recombinant VEGF would have been more efficient in homologous system [human lung explants (5)] but would not have stimulated rat type II cell proliferation because of interspecies differences in responsiveness is unlikely, because 1) it has already been shown previously to exert a variety of biological effects on rat cells (3,34,38) and 2) human recombinant VEGF strongly increased rat SP-B transcripts and delayed type I cell differentiation. The functional significance of the presence of VEGFRs on type II cells, therefore, remains poorly defined.…”

Section: Discussionmentioning

confidence: 99%

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Raoul¹,

Chailley‐Heu²,

Barlier-Mur³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Previous investigations gained from in vivo or lung explant studies suggested that VEGF is an autocrine proliferation and maturation factor for developing alveolar type II cells. The objective of this work was to determine whether VEGF exerted its growth and maturation effects directly on isolated type II cells. These were isolated from 19-day fetal rat lung and cultured in defined medium. The presence of VEGF receptor-2 was assessed in cultured cells at the pre- and posttranslational levels. Recombinant VEGF165, formerly found to be active on lung explants, failed to enhance type II cell proliferation estimated by thymidine and 5-bromo-2′-deoxy-uridine incorporation. It increased choline incorporation in saturated phosphatidylcholine by 27% but did not increase phospholipid surfactant pool size. VEGF (100 ng/ml) left unchanged the transcript level of surfactant proteins (SP)-A, SP-C, and SP-D but increased SP-B transcripts to four times the control steady-state level. VEGF slightly retarded, but did not prevent, the in vitro transdifferentiation of type II into type I cells, as assessed by immunolabeling of the type I cell marker T1α. We conclude that, with the exception of SP-B expression, which appears to be controlled directly, the previously observed effects of this VEGF isoform on type II cells are likely to be exerted indirectly through reciprocal paracrine interactions involving other lung cell types.

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Section: Discussionmentioning

confidence: 99%

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Raoul¹,

Chailley‐Heu²,

Barlier-Mur³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Several receptor tyrosine kinases, including members of the EGF receptor family, EGFR1 and EGFR2, the platelet-derived growth factor receptor, PDGFbR, the insulin-like growth factor type 1 receptor, and the vascular endothelial growth factor receptor, KDR/ Flk-1, are rapidly transactivated following GPCR stimulation (Linseman et al, 1995;Rao et al, 1995;Daub et al, 1996Daub et al, , 1997Tsai et al, 1997;Cunnick et al, 1998;Eguchi et al, 1998;Herrlich et al, 1998;Gschwind et al, 2002;Tanimoto et al, 2002;Thuringer et al, 2002). GPCR-mediated transactivation of EGF receptors frequently accounts for the activation of the ERK1/2 cascade by GPCRs coupled to Gi/o or Gq/11.…”

Section: Gpcr-mediated Transactivation Of Receptor Tyrosine Kinasesmentioning

confidence: 99%

Not so strange bedfellows: G-protein-coupled receptors and Src family kinases

2004

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Src family nonreceptor tyrosine kinases are an integral component of the signal transduction apparatus employed by growth factor receptor tyrosine kinases. As such, their role in cellular growth control and malignant transformation has been the subject of intensive investigation. In contrast, classical G-protein-coupled receptor (GPCR) signaling involves activation of second messenger-regulated serine/threonine kinases or ion channels, and is primarily involved in neurotransmission and the shortterm regulation of intermediary metabolism. Over the past decade, this strictly dichotomous model of transmembrane signaling has been challenged by the discovery that GPCRs also exert control over cellular growth, proliferation, and differentiation, and do so by stimulating tyrosine phosphorylation cascades. Several mechanisms, from the direct association of Src family kinases with GPCRs or receptor-associated proteins, to the transactivation of receptor tyrosine kinases and focal adhesion complexes by G-protein-mediated signals, permit GPCRs to activate Src family kinases. Conversely, Src activity plays a central role in controlling GPCR trafficking and effects on cell proliferation and cytoskeletal rearrangement. It is now clear that GPCRs and Src family kinases do not belong to separate, exclusive clubs. Rather, these strange bedfellows are intimately involved in multilayered forms of crosstalk that influence a host of cellular processes.

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“…The complexity of the protein network governing eNOS activity and trafficking has been highlighted by the recent identification of the eNOS-interacting protein (NOSIP), which binds to the oxygenase domain of eNOS (18). Overexpression of NOSIP triggers eNOS redistribution from the plasma membrane, thereby modulating eNOS activity, most likely by interfering with the membrane-bound caveolin-eNOS complex.Dependent on cell type and͞or mode of stimulation, eNOS has been found to reside in various locales of the cell, including plasma membrane, Golgi apparatus, endoplasmic reticulum, vesicular structures, and even nucleus (19)(20)(21)(22), suggesting that an extensive meshwork of regulatory proteins may surround eNOS. In our quest for previously uncharacterized eNOS partners, we have identified a protein termed eNOS traffic inducer (NOSTRIN) which binds to eNOS and triggers the translocation of eNOS from the plasma membrane to vesicle-like subcellular structures, thereby strongly attenuating eNOS-dependent NO production.…”

mentioning

confidence: 99%

NOSTRIN: A protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase

Zimmermann

Opitz

Dedio

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

162

135

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Activity and localization of endothelial nitric oxide synthase (eNOS) is regulated in a remarkably complex fashion, yet the complex molecular machinery mastering stimulus-induced eNOS translocation and trafficking is poorly understood. In a search by the yeast two-hybrid system using the eNOS oxygenase domain as bait, we have identified a previously uncharacterized eNOS-interacting protein, dubbed NOSTRIN (for eNOS traffic inducer). NOSTRIN contains a single polypeptide chain of 506-aa residues of 58 kDa with an N-terminal cdc15 domain and a Cterminal SH3 domain. NOSTRIN mRNA is abundant in highly vascularized tissues such as placenta, kidney, lung, and heart, and NOSTRIN protein is expressed in vascular endothelial cells. Coimmunoprecipitation experiments demonstrated the eNOS-NOSTRIN interaction in vitro and in vivo, and NOSTRIN's SH3 domain was essential and sufficient for eNOS binding. NOSTRIN colocalized extensively with eNOS at the plasma membrane of confluent human umbilical venous endothelial cells and in punctate cytosolic structures of CHO-eNOS cells. NOSTRIN overexpression induced a profound redistribution of eNOS from the plasma membrane to vesicle-like structures matching the NOSTRIN pattern and at the same time led to a significant inhibition of NO release. We conclude that NOSTRIN contributes to the intricate protein network controlling activity, trafficking, and targeting of eNOS. N itric oxide (NO) is a potent mediator in biological processes such as neurotransmission, inflammatory response, and vascular homeostasis (1). The prime source of NO in the cardiovascular system is endothelial NO synthase (eNOS), which is tightly regulated with respect to activity and localization. For example, coordinated phosphorylation contributes to activity control of eNOS because of activating and inhibiting phosphorylation at S1179 and T495, respectively (2-6). Myristoylation and dual palmitoylation at its extreme N terminus target eNOS to the cytoplasmic face of the Golgi complex and to the plasma membrane (7), where eNOS is thought to be fully capable of activation (8, 9). Misrouting of acylation-deficient eNOS impairs NO production (10, 11), indicating that correct subcellular targeting is critical for stimulus-dependent activation of the enzyme (8). Posttranslational modifications are efficiently complemented by multiple proteinprotein interactions that help regulate eNOS activity with respect to time and space. For instance, chaperone hsp90 bound to eNOS may mediate vascular endothelial growth factor-induced eNOS phosphorylation by promoting the interaction between eNOS and Akt (12, 13). At the plasma membrane, eNOS is complexed to and inhibited by the master components of caveolae, i.e., caveolin-1 in endothelial cells (9, 14) and caveolin-3 in cardiac myocytes (15). After stimulus-induced [Ca 2ϩ ] i increase, the Ca 2ϩ -calmodulin complex displaces eNOS from caveolin (16), stimulates eNOS to produce NO, and subsequently leads to the redistribution of eNOS from plasma membrane caveolae (17). The complexity...

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Rapid Transactivation of the Vascular Endothelial Growth Factor Receptor KDR/Flk-1 by the Bradykinin B2 Receptor Contributes to Endothelial Nitric-oxide Synthase Activation in Cardiac Capillary Endothelial Cells

Cited by 116 publications

References 47 publications

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Not so strange bedfellows: G-protein-coupled receptors and Src family kinases

NOSTRIN: A protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase

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