Mutations in ras proteins. Medical search. Frequent questions

Activating mutations of Ras genes are often observed in cancer. (nature.com)
The protein products of the three Ras genes are almost identical. (nature.com)
Ras genes are mutated in ~20% of all human cancer cases [ 1 ]. (nature.com)
There are three Ras genes that generate four almost identical proteins: HRAS, NRAS, KRAS4A and KRAS4B [ 2 ]. (nature.com)
A cascade effect occurs when ras -GTPase is "switched on" by incoming signals, leading to activation of other proteins, which, in turn, activate genes responsible for cell growth and differentiation. (medscape.com)
Mutations in ras genes can cause permanent activation of ras proteins. (medscape.com)
In this mutation, two genes fuse together to create a new one. (webmd.com)
Your doctor may also mention mutations on the AKT, PTEN, or mTOR genes, which are linked to PIK3CA. (webmd.com)
The proteins produced from these three genes are GTPases. (medlineplus.gov)
We examined: (1) How Ras-MAPK activating variants of PTPN11/SOS1 protein-coding genes affect brain anatomy. (stanford.edu)
The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. (cam.ac.uk)
Activating mutations in Ras genes are found in 33% of human cancers, with Ras well recognized as the most commonly mutated oncogene in human cancer. (aacrjournals.org)
Investigators Marielle Yohe, M.D., Ph.D. , in CCR's Pediatric Oncology Branch and Javed Khan, M.D. , in CCR's Genetics Branch , explored how mutations in the Ras family of genes, cancer-driving mutations that are present in about a third of human tumors, influence the growth of rhabdomyosarcoma. (cancer.gov)
Noonan syndrome and related disorders are caused by mutations in genes encoding for proteins of the RAS-ERK1/2 signaling pathway, which affect development by enhanced ERK1/2 activity. (sdbonline.org)
After a careful selection process, 333 melanoma samples were included in the study, and the screening was conducted using six different platform technologies, going beyond the bounds of simple gene sequencing to explore how the various genes are expressed, how they interact and which proteins they produce. (weizmann.ac.il)
In addition to the sequencing of protein-coding genes, some of the samples had their entire genome sequenced, which could prove in the future to be an "unexplored goldmine of information on what makes cancer tick," says Samuels. (weizmann.ac.il)
Background Mutations in Ras/mitogen-activated protein kinase (Ras/MAPK) pathway genes lead to a class of disorders known as RASopathies, including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). (bmj.com)
Mutations in the three closely related ras genes, H-ras, K-ras, and N-ras, are among the most common mutations found in human cancer, reaching 50% in some types of tumors, such as colorectal carcinoma. (cyberessays.com)
Most mutations in genes are expected to cause their inactivation, however, in the Ras genes the opposite happens - they become more active in signaling. (cyberessays.com)
The Ras family of proteins are enzymes that set in motion the growth, division and differentiation of many types of cells, and their genes have been identified as the most frequently mutated cancer-related genes in humans. (scienceblog.com)
Mutations in Ras genes can lead to the production of permanently activated Ras proteins. (rassignaling.com)
mented genomic RNAs, 2 polymerase genes, PB2 and PA, We conducted a large-scale scanning of infl uenza protein were from the avian virus of North American lineage and sequences and identifi ed amino acid-conserving positions were introduced into swine populations around 1998. (cdc.gov)
[ 6 ] However, the gene mutations responsible for the different forms of CMT1 are clearly myelin genes. (medscape.com)

However, for reasons that remain unclear, KRAS is far more frequently mutated than the other Ras isoforms in cancer and RASopathies. (nature.com)
Finally, direct measurement of mutant versus wildtype KRAS protein abundance revealed a frequent imbalance that may suggest additional non-gene duplication mechanisms for optimizing oncogenic Ras dosage. (nature.com)
76% of Ras-mutant cancer patients harbor KRAS mutations versus only 7% with HRAS mutations [ 1 ]. (nature.com)
Importantly, HRAS, KRAS and NRAS protein abundance was never formally measured in these studies to see whether they conformed with the predicted influence of rare codons. (nature.com)
KRAS mRNA represents 70-99% of all Ras transcripts in mouse tissues [ 20 ]. (nature.com)
We describe here the application of high-resolution melting analysis (HRM) to screen for KRAS mutations in clinical cancer samples. (nih.gov)
In non-small cell lung cancer, KRAS mutations have been shown to identify a group of patients that do not respond to EGFR targeted therapies and the identification of these mutations is thus clinically important. (nih.gov)
We developed a high-resolution melting (HRM) assay to detect somatic mutations in exon 2, notably codons 12 and 13 of the KRAS gene using the intercalating dye SYTO 9. (nih.gov)
We tested 3 different cell lines with known KRAS mutations and then examined the sensitivity of mutation detection with the cell lines using 189 bp and 92 bp amplicons spanning codons 12 and 13. (nih.gov)
We then screened for KRAS mutations in 30 non-small cell lung cancer biopsies that had been previously sequenced for mutations in EGFR exons 18-21. (nih.gov)
Known KRAS mutations in cell lines (A549, HCT116 and RPMI8226) were readily detectable using HRM. (nih.gov)
Nine of the 30 non-small cell lung cancer biopsies had KRAS mutations detected by HRM analysis. (nih.gov)
Mutations in KRAS and EGFR were mutually exclusive. (nih.gov)
Recent research has classified lung adenocarcinoma patients with KRAS mutation into three subtypes by co-occurring genetic events in TP53 (KP subgroup), STK11/LKB1 (KL subgroup) and CDKN2A/B inactivation plus TTF-1 low expression (KC subgroup). (cancerindex.org)
The KRAS gene plays a role in making a protein called K-Ras, which helps cells grow and divide. (webmd.com)
You're more likely to have a KRAS mutation if you have the adenocarcinoma type of NSCLC. (webmd.com)
The contributors review the biochemical characteristics of the different Ras isoforms (HRAS, KRAS, and NRAS), their main effectors and signaling pathways, and the mutations that lead to their constitutive activation. (cshlpress.com)
Initialized and validated with experimental data (including a new structure of active wild-type KRAS), these simulations represent a substantial advance in the ability to characterize RAS-membrane biology. (researchsquare.com)
Although wild-type KRAS4b, a common splice variant of KRAS (hereafter referred to as RAS), does not dimerize on two-component supported lipid bilayers( 16 ), it preferentially co-localizes with anionic lipids in the liquid-disordered domains of giant unilamellar vesicles( 17 ) and the oncogenic G12V mutant clusters on the scale of tens of nanometers in extracted PM sheets( 12, 18 ). (researchsquare.com)
What conclusions about treatment can we draw from EGFR copy number or KRAS mutation status? (ersjournals.com)
Clinical practice in colon cancer also reflects the need for mutational testing to identify patients most likely to benefit from cetuximab: patients whose tumours lack a KRAS mutation (also called wild-type) show significantly increased overall survival (OS) (median 9.5 versus 4.8 months) with cetuximab, whereas those with KRAS mutations do not benefit from therapy 4 . (ersjournals.com)
Approved by the U.S. Food & Drug Administration (FDA) in 2021 after primary analysis of the phase 2 portion of the CodeBreak 100 clinical trial, sotorasib is designed to treat advanced stage NSCLC tumors with the G12C mutation of the KRAS gene when earlier treatment has failed to control the disease. (roswellpark.org)
The KRAS gene produces a protein called K-Ras, which regulates cell growth. (roswellpark.org)
But a KRAS gene mutation called G12C, which represents 13% of NSCLC mutations, can cause cells to grow rapidly and uncontrollably, leading to tumor formation. (roswellpark.org)
There are conflicting data on whether KRAS protein molecules form dimers. (cancer.gov)
And using the same [MEF] system, when we take out the wild type KRAS and put in either oncogenic mutant KRAS or oncogenic KRAS that has the D154Q mutation, we found that in fact the D154Q mutation has a tremendous phenotype both in vitro and in vivo. (cancer.gov)
Scholars@Duke publication: Adenoma-like adenocarcinoma: a subtype of colorectal carcinoma with good prognosis, deceptive appearance on biopsy and frequent KRAS mutation. (duke.edu)
KRAS mutation was seen in 14 of 24 (58%) and four of 17 (24%) were microsatellite-unstable. (duke.edu)
Recent reports have demonstrated that a covalent binder to KRAS protein at a mutated cysteine residue (G12C) is effective for the treatment of solid tumors. (bvsalud.org)
Here, we report a series of 1-{2,7-diazaspiro[3.5]nonan-2-yl}prop-2-en-1-one derivatives as potent covalent inhibitors against KRAS G12C identified throughout structural optimization of an acryloyl amine moiety to improve in vitro inhibitory activity. (bvsalud.org)
From an X-ray complex structural analysis, the 1-{2,7-diazaspiro[3.5]nonan-2-yl}prop-2-en-1-one moiety binds in the switch-II pocket of KRAS G12C. (bvsalud.org)

PJS is autosomal-dominant condition caused by mutations of STK11, characterized by gastrointestinal polyposis, mucocutaneous pigmentation, and predisposition to a range of epithelial cancers: including colorectal, gastric, pancreatic, breast, ovarian cancers and sex cord tumors with annular tubules). (cancerindex.org)
STAT proteins - especially STAT3 and STAT5 - regulate all of these processes and are persistently activated in a surprisingly large number of human cancers. (researchgate.net)
Dafna Bar-Sagi , Saul J. Farber Professor of Biochemistry and Molecular Pharmacology, studies the metabolism of cancers, especially cancers driven by mutations in the RAS protein, which have been linked to 95 percent of pancreatic cancers and nearly one-third of all cancers. (nyu.edu)
Mutations that produce abnormally active Ras proteins are common in human cancers, particularly those of the pancreas, lung, and colon. (cshlpress.com)
These cancers can be difficult to treat because Ras oncoproteins have long been considered undruggable. (cshlpress.com)
This volume is therefore essential reading for all cancer biologists, cell and molecular biologists, and pharmacologists concerned with understanding and treating Ras-driven cancers. (cshlpress.com)
High mobility group B (HMGB) proteins have been previously related to the onset and progressions of cancers of different origins. (hindawi.com)
For instance, NGS-based comprehensive analysis of certain cancers has already helped to uncover specific mutations that contribute to the malignant process, identify new therapeutic targets, and improve opportunities for choosing the best treatment for an individual patient. (biomedcentral.com)
In addition, recent research has found NF1 mutations in a variety of other types of cancers. (iu.edu)
NF1 mutations also affect an important molecular signaling protein called Ras, which, Dr. Clapp noted, is involved with more than a third of all cancers. (iu.edu)
RAS is a signaling protein associated with the cell membrane that is mutated in 30% of human cancers. (researchsquare.com)
RAS driven cancers are common( 1 ), difficult to treat( 2 ), and a major cause of death worldwide( 3 ). (researchsquare.com)
For example, a comparison of genomes from different cancers shows that the genetic mutation pattern of one type of melanoma is similar to that of a form of a brain cancer called glioblastoma. (weizmann.ac.il)
Oncogenic mutations of Ras renders them constitutively active and are associated with ~15% of all human cancers and up to 90% in specific tumors. (itim-cj.ro)
In the paper we go into detail also to show that the mutation doesn't affect some of the other known properties of RAS, membrane localization or nucleotide exchange or GTP hydrolysis, etc., those were not impacted, meaning that we believe that the finding here is truly due to dimerization, and opens some hopefully new therapeutic avenues for RAS mutant cancers. (cancer.gov)
Scientists have breathed new life into the study of a protein with an outsized link to human cancers because of its dangerous mutations, using advanced research techniques to detect its hidden regions. (scienceblog.com)
The subject of this study, the K-Ras protein, is linked to 75% of all Ras-associated cancers. (scienceblog.com)
K-Ras is the holy grail of cancer research - probably one of the most studied biological molecules worldwide because it plays such a key role in many cancers," Brüschweiler said. (scienceblog.com)
PTPN11 mutations also occur in several human cancers, including juvenile myelomonocytic leukaemia (JMML), myelodysplastic syndrome (MDS), B-cell acute lymphoblastic leukaemia (BLL), and acute myelogeneous leukaemia (AML). (lu.se)

This protein negatively regulates the RAS/MAPK pathway, which helps to control cell growth, differentiation and survival. (merck.com)
Michail Steklov, Francesca Baietti, and colleagues from the Anna Sablina lab (VIB-KU Leuven Center for Cancer Biology) identified LZTR1 as an evolutionarily conserved component of the RAS pathway. (news-medical.net)
RASopathy disorders are a group of genetic syndromes caused by mutations in the Ras/mitogen-activated protein (MAPK) pathway. (thermofisher.com)
The RASopathies are genetic syndromes associated with pathogenic variants causing dysregulation of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway, essential for brain development, and increased risk for neurodevelopmental disorders. (stanford.edu)
PTPN11 Mutations in the Ras-MAPK Signaling Pathway Affect Human White Matter Microstructure. (stanford.edu)
Germline activating mutations to the PTPN11 gene cause overactivation of the Ras-Mitogen-Activated Protein Kinase pathway. (stanford.edu)
Scientists have solved the structure of an important complex of RAS-pathway proteins, explaining how known mutations lead to disease and suggesting potential new binding sites for cancer drugs. (broadinstitute.org)
Constitutive activation of oncogenic RAS perturbs several cellular signaling cascades, including the MAPK pathway, which RAS accesses via activation of RAF kinase at the plasma membrane (PM). (researchsquare.com)
Inhibiting an enzyme in the growth-promoting Ras pathway could stop the childhood cancer rhabdomyosarcoma. (cancer.gov)
Their studies, published in Science Translational Medicine , suggest that blocking a protein in the Ras signaling pathway known as MEK may be an effective treatment for the subset of rhabdomyosarcomas that are driven by Ras mutations. (cancer.gov)
A fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome was conducted in a Drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. (sdbonline.org)
This study identified that the protein most commonly affected in Noonan syndrome, the phosphatase SHP2, known in Drosophila as corkscrew (CSW) , controls life span, triglyceride levels, and metabolism without affecting ERK signaling pathway. (sdbonline.org)
This study found that CSW loss-of-function mutations extended life span by interacting with components of the insulin signaling pathway and impairing AKT activity in adult flies. (sdbonline.org)
BRAF and RAS protein products lie in the same pathway so that BRAF and RAS mutations are mutually exclusive: A patient will have one or the other, but not both. (weizmann.ac.il)
Rather, we found that phosphorylated activation loop Y842 serves as a binding site of SHP2, which is required for FLT3-induced activation of RAS/ERK pathway. (lu.se)

Mutations of TSC2 are responsible for tuberous sclerosis, a genetic disorder associated with benign tumors and mental retardation. (uclahealth.org)
Mutations in RAS proteins initiate many of the most aggressive tumors, and the search for pharmacological inhibitors of these proteins has become a priority in the battle against cancer. (news-medical.net)
The Indiana University School of Medicine has been selected to lead a five-year, $12 million national research project to develop new treatments for diseases of a genetic mutation that leads to disfiguring and life-threatening tumors and other developmental disorders, mainly in children. (iu.edu)
K-Ras is the most frequently mutated protein in human tumors. (scite.ai)
RNA and protein expression tests revealed the infiltration of immune cells called lymphocytes into the tumors. (weizmann.ac.il)
Extended response was unaffected by PD-L1 protein levels or STK11 co-mutation, which means sotorasib may be a treatment option for patients whose tumors are unlikely to respond to immunotherapy. (roswellpark.org)
The vast majority (about 90 percent) of pancreatic tumors have mutations in the K-Ras gene. (pancan.org)
RAS inhibition is an effective therapeutic treatment for solid tumors, but RAS protein has been classified as an undruggable target. (bvsalud.org)

These proteins play important roles in cell division, cell differentiation, and the self-destruction of cells (apoptosis). (medlineplus.gov)
The Ras-superfamily G-proteins play critical roles in cell growth and differentiation. (uclahealth.org)
RAS proteins function as molecular switches whose active conformations, stabilized by GTP binding, interact with several protein effectors to control cell growth, proliferation, differentiation, and migration( 10 ). (researchsquare.com)
Yohe's team also conducted detailed experiments to reveal exactly how Ras and MEK affected muscle differentiation. (cancer.gov)
Ras proteins mediate a wide variety of signal transduction pathways that regulate cell growth, proliferation and differentiation. (itim-cj.ro)
RAS protein plays a key role in cellular proliferation and differentiation. (bvsalud.org)
The activating PTPN11 mutations play a broad role in cancer, because SHP-2 acts as a signal-enhancing signalling component in pathways that regulate cell growth, transformation, differentiation, and migration. (lu.se)

[ 2 ] Ras -GTPase is part of a family of related proteins that are universally expressed in cells and are involved in cellular signal transduction. (medscape.com)
Through a process known as signal transduction, the protein relays signals from outside the cell to the cell's nucleus. (medlineplus.gov)
Dr. Fuyu Tamanoi's research focuses on signal transduction involving the Ras-superfamily G-proteins, anti-cancer drugs and nanoparticle-based delivery of anticancer drugs. (uclahealth.org)
The ground-breaking nature of this approach is that it exploits the dynamic nature of Ras nanoclusters and the key role of their stability in signal transduction. (itim-cj.ro)

This protein belongs to the ROCO (ROC and COR domain) protein family and is made up of five characteristic functional domains: leucine-rich repeats (LRR domain), Rasp of complex proteins (ROC domain), C-terminal of Roc (COR domain), mitogen activated protein kinase kinase kinase (MAPKKK domain), and the WD40 domain. (biomedcentral.com)

Here's how some common mutations affect the way your cancer grows, and who's likely to get them. (webmd.com)
The fourth group, called "triple wild type," had none of the three most common mutations. (weizmann.ac.il)
FLT3 mutations emerged as one of the most common mutations in AML which represent around 35% of all AML cases, making it an attractive therapeutic target in AML. (lu.se)

Tamanoi and his colleagues have investigated the function and cellular localization of Ras that is mutated in a wide range of human cancer. (uclahealth.org)
These are as follows: sustained proliferative signalling, cell death resistance, replicative immortality, genome instability and increased mutations, tumour-promoted inflammation, insensibility to growth repressors, deregulation of cellular energetics, evasion of immune destruction, induction of metastasis, and promotion of angiogenesis. (hindawi.com)
While the broad heterogeneity in lateral diffusion observed by SPT (Fig. 1 A) is indicative of multiple RAS sub-populations that have distinct patterns of interaction with lipids and other cellular components, it provides little insights on local lipid environments and their effect on RAS behavior. (researchsquare.com)
Ras proteins are critical regulators of multiple pathways involved in cellular growth control. (aacrjournals.org)
Mutations in Ras associated with cancer promote cellular activation by populating the active state of Ras, most frequently by impairing the action of proteins that downregulate its activity. (aacrjournals.org)
In its active form, GTP-bound RAS is responsible for numerous critical cellular processes. (rcsb.org)
Using structure-guided design, we discovered small molecules that increase nucleotide exchange on RAS in vitro at submicromolar concentrations, bind to SOS1 with low double-digit nanomolar affinity, rapidly enhance cellular RAS-GTP levels, and invoke biphasic signaling changes in phosphorylation of ERK 1/2. (rcsb.org)
This review summarizes the cellular function and pathophysiology of LRRK2 ROCO domain mutations in PD and the perspective of therapeutic approaches. (biomedcentral.com)
The experiments also added clarity to how the normal protein and its mutated forms differ: Under normal circumstances, K-Ras is more active when it is bound to the first of two partner molecules and maintains proper control of multiple cellular functions, including the return to an inactive state. (scienceblog.com)
Instead, the protein product of K-Ras activates a complex cascade of other proteins to ultimately lead to cellular changes. (pancan.org)
Now a large and ever increasing number of genetic subtypes has been described, and major advances in molecular and cellular biology have clarified the understanding of the role of different proteins in the physiology of peripheral nerve conduction in health and in disease. (medscape.com)
Furthermore, Y842 is found to be critical for FLT3-mediated RAS/ERK signaling and cellular transformation. (lu.se)

It is shown here for p21ras, a well studied example of GTP hydrolysing proteins, that the GTP-hydrolysis rate is significantly faster if Mg2+ is replaced by Mn2+, both in the presence or absence of its GTPase-activating protein Ras-GAP. (rcsb.org)
By using Rap1A and Ran, we show that the acceleration of the GTPase by Mn2+ appears to be a general phenomenon of GTP-binding proteins. (rcsb.org)
Although not all functional aspects of neurofibromin 1 are known, it does activate ras -GTPase. (medscape.com)
Consequently, overactive ras -GTPase signaling leads to tumor growth. (medscape.com)
[ 3 ] The neurofibromin 1/ ras -GTPase connection has roles in the control of cell proliferation and the suppression of cell overgrowth. (medscape.com)
The N-Ras protein is a GTPase, which means it converts a molecule called GTP into another molecule called GDP. (medlineplus.gov)
2. Site-Specific Monoubiquitination Activates Ras by Impeding GTPase Activating Protein Function. (aacrjournals.org)
A portion of the Ras protein has an enzyme activity (a GTPase) which cleaves the GTP. (cyberessays.com)
The GTPase is inactivated by the mutations. (cyberessays.com)
Ras mutations involve only certain amino acids, those which interfere with the GTPase function. (cyberessays.com)

HRM will enable high-throughput screening of gene mutations to allow appropriate therapeutic choices for patients and accelerate research aimed at identifying novel mutations in human cancer. (nih.gov)
We hope that the discovery of this alternative mechanism of RAS regulation will lead toward novel therapeutic approaches for RAS-driven diseases. (news-medical.net)
Despite existing knowledge about K-Ras and its key functional relationships with molecules related to cell health, the protein has been deemed "undruggable" because its configuration - both in normal and mutated forms - hides sites in its structure that would be most promising as therapeutic targets. (scienceblog.com)
In this thesis, we have addressed the importance of associating proteins in regulating FLT3 signaling as well as identified novel therapeutic targets to overcome FLT3-related resistance. (lu.se)

The NF1 phenotype is highly penetrant (ie, almost all individuals with an NF1 gene mutation have some phenotypic traits of the syndrome). (medscape.com)
The type of gene mutation you have often depends on what kind of lung cancer you have. (webmd.com)
Anyone can get a gene mutation that causes lung cancer. (webmd.com)
RAS gene mutation is a known driver of oncogenic alternation in human cancer. (bvsalud.org)

The main objective of this application is the development of a new approach on finding potential drugs against oncogene Ras. (itim-cj.ro)

Activating mutations cause Noonan syndrome (NS), a developmental disorder associated with hyperactivity and cognitive weakness in attention, executive function, and memory. (stanford.edu)
We find that this activating mutation introduces a redox active cysteine that renders Ras G12C sensitive to thiol oxidation. (aacrjournals.org)
Although a number of studies have shown that patients with activating mutations in exons 18-21 of the epidermal growth factor receptor (EGFR) gene respond particularly well to gefitinib and erlotinib, a prospective, randomised study was needed to differentiate between the prognostic and predictive value of EGFR mutations. (ersjournals.com)
Activating K-Ras mutations drive cancer initiation, progression and drug resistance, directly leading to nearly a million deaths per year. (scite.ai)

The fundamental challenge of investigating RAS activation events is that many of the proposed mechanisms involve time- and lengths scales currently not accessible. (researchsquare.com)

This is currently best expressed in the Ras "sweet-spot" model that suggests that Ras dosage (expression and signaling strength imparted by specific mutations) will be a major factor in influencing the availability of individual Ras family members to engage cancer pathways [ 4 ]. (nature.com)
There are new drugs, called targeted therapy, that zero in on the specific mutations you have. (webmd.com)

This involves both farnesylation (catalyzed by protein farnesyltransferase) and geranylgeranylation (catalyzed by protein geranylgeranyltransferase-I). Small molecular inhibitors of protein geranylgeranyltransferase-I were identified from a library of compounds generated by phosphine catalysis of allenoate compounds. (uclahealth.org)
They can be combined with farnesyltransferase inhibitors to block the function of K-Ras proteins. (uclahealth.org)
Recent work showing that some Ras oncoproteins may be effectively inhibited by small molecules is covered, as is work on alternative targets (e.g., enzymes that catalyze posttranslational modifications of Ras) and inhibitors (e.g., nucleic acids). (cshlpress.com)
Only recently, with the development of covalent inhibitors of the G12C mutant( 6 ), has direct targeting of RAS been successful, and more broadly applicable inhibitors are needed. (researchsquare.com)

The NF1 phenotype results from loss-of-function mutations of the NF1 gene and, therefore, the absence of neurofibromin 1. (medscape.com)

At the most fundamental level it must relate to the opportunity and capacity of each Ras isoform to interact with and activate key effector pathways. (nature.com)
What pathways are this gene/protein implicaed in? (cancerindex.org)
Ras proteins are key molecular switches in cell signaling pathways that, when activated, trigger cell growth and division. (cshlpress.com)
The protein is also required for normal Ras activation in many of these pathways. (lu.se)

We provide evidence for the effects of Ras-MAPK pathogenic variants on striatal and cortical anatomy as well as links between PTPN11 gene expression and cortical SA increases, and striatal volume and inhibition skills. (stanford.edu)
These findings provide essential translational information on the Ras-MAPK pathway's effect on human brain development and function. (stanford.edu)
Previous work has suggested potential genetic and phenotypic overlap between dysregulation of Ras/MAPK signalling and autism spectrum disorders (ASD). (bmj.com)
Although the literature offers conflicting evidence for association of NF1 and autism, there has been no systematic evaluation of autism traits in the RASopathies as a class to support a role for germline Ras/MAPK activation in ASDs. (bmj.com)
Conclusions Higher prevalence and severity of autism traits in RASopathies compared to unaffected siblings suggests that dysregulation of Ras/MAPK signalling during development may be implicated in ASD risk. (bmj.com)

Oncogenic mutations or abnormal expression of signaling components disrupt the regulatory networks that govern cell function, thus enabling tumor cells to undergo dysregulated mitogenesis, to resist apoptosis, and to promote invasion to neighboring tissues. (eurekaselect.com)
However, despite decades of research, how oncogenic mutations in K-Ras alter its conformation and dynamics remain to be understood. (scite.ai)

These mutations lead to production of an N-Ras protein that is constantly turned on (constitutively active). (medlineplus.gov)
These mutations lead to an N-Ras protein that is constitutively active and can direct cells to grow and divide without control. (medlineplus.gov)

By introducing cancer-causing mutations into healthy skin cells step-by-step, Broad scientists have created models of skin cancer that can reveal the effects of mutations. (broadinstitute.org)

We will also present our recent work on an oncogenic variant prevalent in lung cancer, K-Ras G12C. (aacrjournals.org)
Sotorasib, which blocks G12C, is the first FDA-approved therapy for a malignancy targeted specifically against K-RAS mutation. (roswellpark.org)

Ras-interacting protein 1 (Rain), is a protein that in humans is encoded by the RASIP1 gene. (wikipedia.org)

Mutations in the NF1 gene may result in dysregulation in RAS/RAF/MEK/ERK signaling, which can cause cells to grow, divide and copy themselves in an uncontrolled manner, and may result in tumor growth. (merck.com)

Patients with LRRK2 mutations exhibit a clinical and pathological phenotype indistinguishable from sporadic PD. (biomedcentral.com)
PHENOTYPE: Mice homozygous for a targeted mutation exhibit complete embryonic lethality during organogenesis associated with a failure in cardiovascular development. (utsouthwestern.edu)
PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. (lu.se)
Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome. (lu.se)

These findings represent a paradigm shift in our understanding of the role monoubiquitination may play in protein regulation as well as new mechanisms for regulation of Ras activity. (aacrjournals.org)
We find that monoubiquitination of K- and H-Ras occurs at distinct sites, both of which can upregulate Ras activity, but by different mechanisms [2-4]. (aacrjournals.org)
To understand the mechanisms by which mutations alter K-Ras function, we need to understand their effects on protein dynamics. (scite.ai)
It is concluded that CSW normally regulates life span and that mutations in SHP2 are expected to have critical effects throughout life by insulin-dependent mechanisms in addition to the well-known RAS-ERK1/2-dependent developmental alterations. (sdbonline.org)
We know that structural biology can provide unique insights into the mechanisms of those mutations and can stimulate the search for potential cures. (scienceblog.com)

This gene controls a protein called "epidermal growth factor receptor. (webmd.com)
Ras signaling can be thought of in simple terms as occuring downstream of receptor tyrosine kinases, triggered by association of adaptor proteins with the phosphorylated cytoplasmic tails of these receptors. (sdbonline.org)
These data revealed an unexpected direct binding of Corkscrew, the Drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e , the human ortholog of the p110 catalytic subunit. (sdbonline.org)
Rapid emergence of spike receptor binding domain mutations was found, associated with a compartmentalization of viral populations. (cdc.gov)
Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. (who.int)

Among these mutations, FLT3-ITD is associated with a high risk of relapse and poor prognosis. (lu.se)

The N-Ras protein acts like a switch, and it is turned on and off by the GTP and GDP molecules. (medlineplus.gov)
HMGB1 is an abundant protein, 10 6 molecules per cell [ 7 ], which has been postulated as a redox sensor [ 8 ]. (hindawi.com)
There is substantial interest in assessing the ability of RAS molecules to dimerize( 11 ) or co-localize( 12 ) at the membrane, because RAS-dependent RAF activation requires dimerization of RAF( 13-15 ). (researchsquare.com)
Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange. (rcsb.org)

Somatic mutations in the NRAS gene are involved in the development of several types of cancer. (medlineplus.gov)
Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. (lu.se)

To determine the mechanism by which ubiquitination activates Ras, we conducted NMR, modeling, biochemical and biological studies of monoubiquitinated H-Ras and K-Ras. (aacrjournals.org)

Tamanoi's laboratory has developed anti-cancer drugs against Ras proteins aimed at inhibiting their posttranslational modification and membrane association. (uclahealth.org)
This conjugation reduces RAS recruitment to the membrane and thus its activation and downstream signaling. (news-medical.net)
RAS signaling has been proposed to be regulated by dynamic heterogeneity of the cell membrane. (researchsquare.com)
The RAS subfamily comprises peripheral membrane proteins with a conserved globular GTP-binding domain (G-domain)( 7 ) that is tethered to the cell membrane by a prenylated ~ 20 residue C-terminal domain called the hypervariable region (HVR)( 8, 9 ). (researchsquare.com)
Experiments and computer simulations alike showed that membrane-bound Ras proteins form non-overlapping dynamic nano-sized subdomains (nanoclusters) in an activation state-/isoform-dependent manner. (itim-cj.ro)
These ectatic vessels are lined by flat, benign-appearing endothelial cells, similar to the vessels of normal skin, with similar staining characteristics for endothelial antigens, including fibronectin, von Willebrand factor, and collagenous basement membrane proteins. (medscape.com)
Cystic fibrosis (CF) is an autosomal recessive condition caused by the mutation of the cystic fibrosis trans-membrane regulator gene (CFTR) on chromosome 7. (who.int)

The initial hits are optimized by structure-based design, resulting in potent RAS-binding compounds that interact with RAS inside the cells, prevent RAS-effector interactions and inhibit endogenous RAS-dependent signalling. (nih.gov)
Frank, would you like to summarize the data from your lab, and from the RAS Initiative here at the FNL, that have influenced your thinking about how RAS proteins might interact? (cancer.gov)
Brüschweiler has his own thoughts on what might come next, such as describing how existing drugs interact with the protein. (scienceblog.com)

Structure of the functional domain of the LRRK2 protein and the pathogenic mutations associated with PD. (biomedcentral.com)

Lower levels of expression will influence relative activity and be insufficient to initiate tumorigenesis, whilst too much Ras will induce oncogenic stress. (nature.com)
Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine covers the recent progress that has been made in understanding Ras biology, how Ras activation leads to tumorigenesis, and ways in which oncogenic Ras signaling may be targeted therapeutically. (cshlpress.com)
It has recently been shown that K-Ras monoubiquitination, upregulates its activity by populating the active GTP-bound state, enhances interactions with certain downstream effectors and promotes Ras-mediated tumorigenesis [1]. (aacrjournals.org)

This genetic mutation is innate, and clinical symptoms appear early in life and continue over many years. (medscape.com)

Mutations in PTPN11 cause Noonan syndrome (NS), a developmental disorder characterized by facial dysmorphisms, short stature, skeletal and haematological defects, and cardiovascular abnormalities. (lu.se)
Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. (lu.se)

We have quantified HRAS, NRAS, KRAS4A and KRAS4B protein abundance across a large panel of cell lines and healthy tissues. (nature.com)
NRAS»HRAS protein expression in cells that correlate with the rank order of Ras mutation frequencies in cancer. (nature.com)
We suggest that in most cases, being the most abundant Ras isoform correlates with occupying the sweet-spot and that HRAS and NRAS expression is usually insufficient to promote oncogenesis when mutated. (nature.com)
The NRAS gene provides instructions for making a protein called N-Ras that is involved primarily in regulating cell division. (medlineplus.gov)
At least two mutations in the NRAS gene have been found to cause giant congenital melanocytic nevus. (medlineplus.gov)
The NRAS gene mutations that cause this condition are somatic, meaning that they occur during a person's lifetime and are present only in certain cells. (medlineplus.gov)
Studies suggest that NRAS gene mutations are common in the aggressive skin cancer melanoma, including individuals without giant congenital melanocytic nevus (described above). (medlineplus.gov)
Mutations in the NRAS gene have also been found in other types of cancer. (medlineplus.gov)
For reasons that are unclear, inherited mutations in the NRAS gene do not appear to increase the risk of cancer in people with Noonan syndrome. (medlineplus.gov)

The researchers found that LZTR1 contributes to human diseases by acting as a part of the ubiquitin ligase complex that mediates conjugation of ubiquitin to RAS proteins. (news-medical.net)
We examined whether PTPN11 mutations affect the white matter connectivity of the developing human brain. (stanford.edu)
In mouse models of NS, PTPN11 mutations cause reduced axon myelination and white matter formation, while the effects of PTPN11 mutations on human white matter are largely unknown. (stanford.edu)
This review describes recent advances in the role of human HMGB proteins and other proteins interacting with them, in cancerous processes related to oxidative stress, with special reference to ovarian and prostate cancer. (hindawi.com)
The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (human GAB2 but not Drosophila Dos ). (sdbonline.org)
In Drosophila disease models, this study found both SHP2 mutations from human patients and corkscrew (csw) homolog LoF/GoF elevate glutamatergic transmission. (sdbonline.org)
A lately developed and validated immunotagging technique makes use of three transcription issue antibodies to concurrently isolate enriched neuronal (NeuN+), astrocyte (paired field protein 6 (PAX6)+NeuN-), and oligodendrocyte progenitor ( OLIG2 +NeuN-) nuclei populations from non-diseased, recent (unfixed) snap-frozen postmortem human temporal neocortex tissue. (aetox.com)

This dominantly acting mutation in ras results in its constitutive activation and. (cyberessays.com)

Prevalence and architecture of de novo mutations in developmental disorders. (cam.ac.uk)

Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. (sdbonline.org)

Now melanoma researchers will be able to focus on understanding exactly how the different mutations lead to cancer, and physicians may eventualy gain better tools for diagnosing the disease and tailoring treatments to individual cases. (weizmann.ac.il)
Acute myeloid leukemia (AML) is a highly heterogeneous blood disease which is characterized by different mutations and chromosomal rearrangements. (lu.se)

The ras signal is turned off by a molecular switch, which depends on an enzyme activity. (cyberessays.com)

While Noonan syndrome can be inherited, de novo or spontaneous mutations account for nearly 60% of diagnosed cases. (thermofisher.com)
Noonan syndrome (NS) and NS with multiple lentigines (NSML) cognitive dysfunction are linked to SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) gain-of-function (GoF) and loss-of-function (LoF), respectively. (sdbonline.org)

Targeting specific protein-protein interactions (PPIs) is an attractive concept for drug development, but hard to implement since intracellular antibodies do not penetrate cells and most small-molecule drugs are considered unsuitable for PPI inhibition. (nih.gov)
2016) . A cross-species study of PI3K protein-protein interactions reveals the direct interaction of P85 and SHP2 . (sdbonline.org)
Researchers at The Ohio State University are the first to detect a section of this protein's structure that had previously been unobservable by standard lab tools, revealing features and interactions related to the protein's mutations that put cells into a state of perpetual division - a classic cancer characteristic. (scienceblog.com)
Standard NMR can follow a fast-acting protein but has trouble with a longer time scale of movement and interactions, and X-ray crystallography used to define protein structures does better with less movement and more time. (scienceblog.com)
Sanowar S, Singh P, Pfuetzner RA, Andre I, Zheng H, Spreter T, Strynadka NC, Baker D, Goodlett DR and Miller S. Interactions of the Transmembrane Polymeric Rings of the Salmonella enterica Serovar Typhimurium Type III Secretion System. (lu.se)

The mutations occur during embryonic development in cells that will develop into pigment-producing skin cells (melanocytes). (medlineplus.gov)
Mutations of the K-Ras gene occur in over 90% of pancreatic carcinomas. (cyberessays.com)
Mutations in K-ras occur early in the development of colon carcinoma. (cyberessays.com)
The study revealed two "switch" regions - tellingly, both located near a protein loop where the most dangerous mutations occur - in the K-Ras structure that had not been visible before. (scienceblog.com)

Changes in the redox state of cells affect proteins, lipids, and nucleic acids in different ways. (hindawi.com)

An EGFR mutation is more common in women, people who don't smoke, and those with the adenocarcinoma type of NSCLC. (webmd.com)

Microfilaments, microtubules, and intermediate filaments serve as the cytoskeleton of the cell and form a complex network by interacting with cytoskeleton-associated proteins. (doria.fi)
We started hypothesizing that the most obvious interpretation of interference was from subunit poisoning by wild type proteins with mutant proteins into complexes, where maximum signal output would require both the proteins to be in the active state persistently, and that having a wild type protein would be like a sort of flat tire and would be a much less efficient complex than a sort of double barreled mutant RAS. (cancer.gov)
The team also established the complex structural dynamics behavior of the protein "backbone" that amplified additional features close to the switches. (scienceblog.com)

HRM is a sensitive in-tube methodology to screen for mutations in clinical samples. (nih.gov)

Recent studies have shown that pathological mutations of LRRK2 can reduce the rate of guanosine triphosphate (GTP) hydrolysis, increase kinase activity and GTP binding activity, and subsequently cause cell death. (biomedcentral.com)

If the mutation in a gene, for example, a tumor suppressor, causes a loss of function, you can't fix it by blocking the gene - the problem is that the gene is not working in the first place," she says. (weizmann.ac.il)
Mutation of the p53 tumor suppressor gene is considered to be one of the steps leading to the neoplastic state. (cdc.gov)

LRRK2 is a large gene spanning a genomic region of 144 kb with 51 exons and encodes a multidomain protein consisting of 2527 amino acids. (biomedcentral.com)

Even less is known about the influence of RAS-lipid coupling on RAS self-assembly and effector activation. (researchsquare.com)
1. Ubiquitination of K-Ras enhances activation and facilitates binding to select downstream effectors. (aacrjournals.org)
Nanoclusters are protein-lipid assemblies serving as exclusive sites for effector recruiting and signal activation. (itim-cj.ro)

While several feasible dimer interfaces have been reported( 11, 21-24 ), how RAS forms dimers, if at all, remains a major area of interest. (researchsquare.com)
Two authors of the latter paper, Pasi Jänne and Chiara Ambrogio, recently discussed the issue of RAS dimers with Frank McCormick, who is advising the NCI RAS Initiative at the Frederick National Lab. (cancer.gov)

How does a family of Ras proteins that share a common set of activators and effectors generate isoform-specific engagement with cancer-associated signaling networks? (nature.com)

Anatomy13

Organisms14

Diseases8

Chemicals and Drugs99

Analytical, Diagnostic and Therapeutic Techniques and Equipment26

Phenomena and Processes95

Disciplines and Occupations1

Information Science3

Named Groups2

Health Care4

Genes23

KRAS31

Cancers19

Pathway15

Tumors8

Differentiation7

Signal Transduction4

Mitogen-activa1

Common mutations3

Cellular12

GTPase10

Therapeutic4

Gene mutation4

Oncogene1

Activating4

Investigating RAS activation1

Specific mutations2

Inhibitors4

Loss-of-function mutati1

Pathways4

MAPK5

Oncogenic mutations2

Constitutively active2

Cancer-causing m1

G12C2

Humans1

Dysregulation1

Phenotype4

Mechanisms5

Receptor5

Prognosis1

Molecules4

Somatic mutations2

Activates1

Membrane7

Interact3

Pathogenic1

Tumorigenesis3

Genetic mutation1

Cause Noonan syndrome2

NRAS9

Human7

Constitutive activation1

Novo mutations1

Adaptor proteins1

Different mutations2

Molecular1

Noonan2

Interactions5

Occur4

Nucleic acids1

EGFR1

Complex3

Clinical1

Kinase1

Tumor suppressor2

Amino acids1

Activation3

Dimers2

Effectors1