Sprouty4 levels are increased under hypoxic conditions by enhanced mRNA stability and transcription
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Barbara Haigl
Abstract
Sprouty (Spry) proteins are well-known negative regulators of receptor tyrosine kinase-mediated signalling. Their expression is controlled by mitogens, implying a negative feedback loop. Correspondingly, the different members of the family fulfil important roles during organogenesis by adjustment of growth factor-induced processes. In addition, Spry4, one member of this protein family, has been shown to regulate angiogenesis by inhibiting vascular endothelial cell growth factor-induced extracellular signalling-regulated kinase (ERK) activation. Because oxygen is an important regulator of angiogenesis, we investigated Spry4 expression patterns under hypoxic conditions. Our data demonstrate that both hypoxia and desferrioxamine (DFO) treatment increased Spry4 expression. Following iron depletion, elevated Spry4 levels were detected in several cell types independent of tissue origin, presence of mitogens, cell differentiation and malignancy. Evaluation of the underlying regulative mechanisms revealed that augmented transcription and increased mRNA stability enhance mRNA levels of Spry4 in response to DFO. This study unveils a growth factor-independent regulation mechanism of Spry4 expression. Because increased Spry4 levels are accompanied by disappearing ERK phosphorylation, Spry4 might be involved in the timely restriction of MAPK signals under hypoxic conditions, similar to its role in mitogen-regulated processes. However, the functional significance of the observed upregulation of Spry4 during iron depletion remains to be clarified.
©2010 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Guest Editorial
- Highlight: Of Systems and Structures
- HIGHLIGHT: STRUCTURAL SYSTEMS BIOLOGY
- Converging on the function of intrinsically disordered nucleoporins in the nuclear pore complex
- Towards molecular systems biology of gene transcription and regulation
- Small-angle X-ray and neutron scattering as a tool for structural systems biology
- The type III secretion injectisome, a complex nanomachine for intracellular ‘toxin’ delivery
- Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates
- The XPD helicase: XPanDing archaeal XPD structures to get a grip on human DNA repair
- Decoding transcription and microRNA-mediated translation control in Drosophila development
- Human SepSecS or SLA/LP: selenocysteine formation and autoimmune hepatitis
- PROTEIN STRUCTURE AND FUNCTION
- The rhodanese RhdA helps Azotobacter vinelandii in maintaining cellular redox balance
- MEMBRANES, LIPIDS, GLYCOBIOLOGY
- The membrane-bound bile acid receptor TGR5 (Gpbar-1) is localized in the primary cilium of cholangiocytes
- CELL BIOLOGY AND SIGNALING
- miR-221/222 suppression protects against endoplasmic reticulum stress-induced apoptosis via p27Kip1- and MEK/ERK-mediated cell cycle regulation
- Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway
- Sprouty4 levels are increased under hypoxic conditions by enhanced mRNA stability and transcription
- PROTEOLYSIS
- Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.
- NOVEL TECHNIQUES
- Detection of breast cancer-related antigens through cDNA phage-displayed protein microarray
