scholarly journals Equilibria between conformational states of the Ras oncogene protein revealed by high pressure crystallography

2022 ◽  
Author(s):  
Eric Girard ◽  
Rui P Lopes ◽  
Michael Spoerner ◽  
Anne-Claire Dhaussy ◽  
Thierry Prangé ◽  
...  
Keyword(s):  
High Pressure ◽  
Small Gtpase ◽  
Ras Oncogene ◽  
Conformational States ◽  
Ras Protein ◽  
Allosteric Transitions ◽  
High Pressure Crystallography ◽  
Oncogene Protein

In this work, we experimentally investigate the allosteric transitions between conformational states on the Ras oncogene protein using high pressure crystallography. Ras protein is a small GTPase involved in central...

Role of phosphatidylinositide metabolism in ras-induced Xenopus oocyte maturation

1990 ◽  
Vol 10 (3) ◽  
pp. 923-929
Author(s):  
B T Pan ◽  
G M Cooper
Keyword(s):  
Xenopus Oocytes ◽  
Second Messengers ◽  
Phospholipid Metabolism ◽  
Meiotic Maturation ◽  
Ras Oncogene ◽  
Ras Protein ◽  
32P Incorporation ◽  
Kinetics Of ◽  
Oncogene Protein

Microinjection of Xenopus oocytes with ras protein (p21) was used to investigate the role of phospholipid metabolism in ras-induced meiotic maturation. Induction of meiosis by ras was compared with induction by progesterone, insulin, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Neomycin, which specifically binds to phosphatidylinositides and inhibits their metabolism, blocked meiotic maturation induced by ras or insulin but not by progesterone or TPA. In addition, p21 and TPA, but not insulin or progesterone, stimulated the incorporation of 32Pi into oocyte lipids. ras protein specifically stimulated 32P incorporation into phosphatidylinositides, whereas both ras and TPA stimulated 32P incorporation into phosphatidylcholine and phosphatidylethanolamine. The stimulatory effect of p21 on phosphatidylinositide metabolism correlated with the dose response and kinetics of ras-induced meiotic maturation. In addition, the ras oncogene protein was more potent than the proto-oncogene protein both in inducing meiotic maturation and in stimulating phosphatidylinositide metabolism. These results indicate that phosphatidylinositide turnover is required for ras-induced meiosis and suggest that phosphatidylinositide-derived second messengers mediate the biological activity of ras in Xenopus oocytes.

scholarly journals Role of phosphatidylinositide metabolism in ras-induced Xenopus oocyte maturation.

1990 ◽  
Vol 10 (3) ◽  
pp. 923-929 ◽  
Author(s):  
B T Pan ◽  
G M Cooper
Keyword(s):  
Xenopus Oocytes ◽  
Second Messengers ◽  
Phospholipid Metabolism ◽  
Meiotic Maturation ◽  
Ras Oncogene ◽  
Ras Protein ◽  
32P Incorporation ◽  
Kinetics Of ◽  
Oncogene Protein

Microinjection of Xenopus oocytes with ras protein (p21) was used to investigate the role of phospholipid metabolism in ras-induced meiotic maturation. Induction of meiosis by ras was compared with induction by progesterone, insulin, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Neomycin, which specifically binds to phosphatidylinositides and inhibits their metabolism, blocked meiotic maturation induced by ras or insulin but not by progesterone or TPA. In addition, p21 and TPA, but not insulin or progesterone, stimulated the incorporation of 32Pi into oocyte lipids. ras protein specifically stimulated 32P incorporation into phosphatidylinositides, whereas both ras and TPA stimulated 32P incorporation into phosphatidylcholine and phosphatidylethanolamine. The stimulatory effect of p21 on phosphatidylinositide metabolism correlated with the dose response and kinetics of ras-induced meiotic maturation. In addition, the ras oncogene protein was more potent than the proto-oncogene protein both in inducing meiotic maturation and in stimulating phosphatidylinositide metabolism. These results indicate that phosphatidylinositide turnover is required for ras-induced meiosis and suggest that phosphatidylinositide-derived second messengers mediate the biological activity of ras in Xenopus oocytes.

scholarly journals Placental Ras Regulates Inflammation Associated with Maternal Obesity

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Stella Liong ◽  
Gillian Barker ◽  
Martha Lappas
Keyword(s):  
Protein Expression ◽  
Pregnant Women ◽  
Human Placenta ◽  
Maternal Obesity ◽  
Small Gtpase ◽  
Obese Women ◽  
Trophoblast Cells ◽  
Ras Protein ◽  
Placental Inflammation ◽  
Expression And Activity

Heightened placental inflammation and dysfunction are commonly associated in pregnant obese women compared to their pregnant lean counterparts. The small GTPase superfamily members known as the rat sarcoma viral oncogene homolog (Ras) proteins, in particular, the K-Ras and H-Ras isoforms, have been implicated to regulate inflammation. The aims were to determine the placental Ras expression and activity with maternal obesity and its role in regulating placental inflammation. Human placenta was obtained at term Caesarean section from lean and obese pregnant women to determine the effect of maternal obesity on Ras protein expression and activity. To determine the effect of Ras on inflammation induced by bacterial endotoxin LPS and proinflammatory cytokines TNF-α or IL-1β, the chemical inhibitor lonafarnib (total Ras inhibitor) and siRNA (siKRAS and siHRAS) were used. Total Ras protein expression together with combined K-Ras and H-Ras activity was significantly increased in the placenta of obese pregnant women and when stimulated with LPS, IL-1β, or TNF-α. Lonafarnib significantly suppressed LPS-, IL-1β-, or TNF-α-induced IL-6, IL-8, MCP-1, and GRO-α expression and secretion in placental tissue. Primary trophoblast cells transfected with siKRAS or siHRAS demonstrated only K-Ras silencing significantly decreased IL-1β-, TNF-α-, or LPS-induced IL-6, IL-8, and MCP-1 expression and secretion. Furthermore, siKRAS significantly reduced downstream ERK-1/2 activation induced by LPS. In trophoblast cells, ERK-1/2 signalling is required for IL-6, IL-8, MCP-1, and GRO-α secretion. These studies implicate a role for K-Ras in regulating inflammation in human placenta. Suppressing overactive placental K-Ras function may prevent adverse fetal outcomes complicated by maternal obesity.

scholarly journals Analysis of RAS protein interactions in living cells reveals a mechanism for pan-RAS depletion by membrane-targeted RAS binders

2020 ◽  
Vol 117 (22) ◽  
pp. 12121-12130
Author(s):  
Yao-Cheng Li ◽  
Nikki K. Lytle ◽  
Seth T. Gammon ◽  
Luke Wang ◽  
Tikvah K. Hayes ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Developmental Disorders ◽  
Degradation Pathway ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Ras Proteins ◽  
Ras Protein ◽  
Protein Levels ◽  
Ras Family ◽  
Ras Isoforms

HRAS, NRAS, and KRAS4A/KRAS4B comprise the RAS family of small GTPases that regulate signaling pathways controlling cell proliferation, differentiation, and survival. RAS pathway abnormalities cause developmental disorders and cancers. We found that KRAS4B colocalizes on the cell membrane with other RAS isoforms and a subset of prenylated small GTPase family members using a live-cell quantitative split luciferase complementation assay. RAS protein coclustering is mainly mediated by membrane association-facilitated interactions (MAFIs). Using the RAS–RBD (CRAF RAS binding domain) interaction as a model system, we showed that MAFI alone is not sufficient to induce RBD-mediated RAS inhibition. Surprisingly, we discovered that high-affinity membrane-targeted RAS binding proteins inhibit RAS activity and deplete RAS proteins through an autophagosome–lysosome-mediated degradation pathway. Our results provide a mechanism for regulating RAS activity and protein levels, a more detailed understanding of which should lead to therapeutic strategies for inhibiting and depleting oncogenic RAS proteins.

Tracking conformational states in allosteric transitions of phosphorylase

Biochemistry ◽  
1992 ◽  
Vol 31 (46) ◽  
pp. 11297-11304 ◽  
Author(s):  
Michelle F. Browner ◽  
Eric B. Fauman ◽  
Robert J. Fletterick
Keyword(s):  
Conformational States ◽  
Allosteric Transitions

scholarly journals Structural Rigidity of a Large Cavity-containing Protein Revealed by High-pressure Crystallography

2007 ◽  
Vol 367 (3) ◽  
pp. 752-763 ◽  
Author(s):  
Marcus D. Collins ◽  
Michael L. Quillin ◽  
Gerhard Hummer ◽  
Brian W. Matthews ◽  
Sol M. Gruner
Keyword(s):  
High Pressure ◽  
Large Cavity ◽  
Structural Rigidity ◽  
High Pressure Crystallography

High-pressure crystallography and compression behavior of the alkali-scandium-germanate end-members LiScGe2O6 and NaScGe2O6

2015 ◽  
Vol 229 ◽  
pp. 188-196 ◽  
Author(s):  
Gregor Hofer ◽  
Johann Kuzel ◽  
Katharina S. Scheidl ◽  
Günther Redhammer ◽  
Ronald Miletich
Keyword(s):  
High Pressure ◽  
Compression Behavior ◽  
High Pressure Crystallography ◽  
End Members

scholarly journals Structure-properties relationship in Borinic Systems at high and normal pressure

2014 ◽  
Vol 70 (a1) ◽  
pp. C1264-C1264
Author(s):  
Grzegorz Wesela-Bauman ◽  
Simon Parsons ◽  
Sergiusz Luliński ◽  
Janusz Serwatowski ◽  
Krzysztof Woźniak
Keyword(s):  
High Pressure ◽  
Normal Pressure ◽  
Organic Light Emitting Diodes ◽  
Theoretical Evaluation ◽  
Light Emitting ◽  
Orbital Interactions ◽  
High Pressure Crystallography ◽  
The Impact ◽  
Polymorph Screening ◽  
Structure Properties

Recently we were focused on the synthetic, physicochemical and theoretical evaluation of the properties of borinic 8-oxyquinolinates.[1,2] Such systems are of interest of many groups in the world, as borinic derivatives are promising materials for the preparation of luminescent layers in organic light emitting diodes (OLEDs).[3] Our aim is to trace the impact of structure on properties of the system. Hence we have conducted polymorph screening for highly strain aromatic heteroleptic borinic system. As a result, we are presenting, the very first examples of polymorphism in the group of aromatic borinic 8-oxyquinolinate complexes [(2-fluoro-3-pyridyl) (2,2`-biphenyl)borinic 8-oxyquinolinate)]. We wanted to extend our investigations on high-pressure crystallography. These investigations were prompted by results obtained by other groups which analysed crystal structures of AlQ3, GaQ3 and InQ3 under low and high pressure. Such studies helped to trace a connection between the motifs present in the crystal phases and optical properties of these complexes as a consequence of orbital interactions. On this basis we were interested in investigation of the influence of high pressure on the packing of synthesized and characterized (2-fluoro-3-pyridyl) (4-iodophenyl)borinic 8-oxyquinolinate.

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