The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The requested target is unambiguously human ARAF, encoding A-Raf, UniProt P10398—not an ARAF pseudogene or a similarly named non-human protein. The supplied description, aliases (ARAF1, PKS, PKS2), serine/threonine-protein-kinase classification, and C1-like/DAG-binding plus protein-kinase domains agree with the literature on the ARAF member of the three-protein RAF family. Open Targets likewise maps approved symbol ARAF to human gene ENSG00000078061 and distinguishes it from ARAFP2, an ARAF pseudogene (OpenTargets Search: -ARAF).
ARAF’s primary molecular function is to act as a RAS-regulated MAP kinase kinase kinase. It transfers the γ-phosphate of ATP to serine/threonine residues in MEK1/MAP2K1 and MEK2/MAP2K2, promoting MEK-dependent activation of ERK1/2. Wild-type ARAF is the least catalytically active RAF paralog under many assay conditions, but activated dimers and disease mutants can signal strongly. ARAF also has important non-catalytic functions, particularly sequestration of the pro-apoptotic kinase MST2 at mitochondria. Its location and function are consequently state-dependent: inactive cytosolic complexes, RAS-associated plasma-membrane signalosomes, trafficking compartments, and mitochondria are all relevant.
| Feature | Best-supported annotation | Evidence type | Key source/date |
|---|---|---|---|
| Identity and domains | Human ARAF encodes A-Raf, one of three RAF-family serine/threonine kinases. Conserved regions comprise CR1 (RAS-binding and cysteine-rich/C1-like membrane-binding domains), regulatory CR2, and CR3 (protein-kinase domain); unlike BRAF, ARAF lacks the BRAF-specific region. This matches UniProt P10398 and the stated TKL kinase, C1-like/DAG-binding, and kinase-domain annotations. | Curated target identity plus comparative sequence/structural analysis | Jeon, Tkacik & Eck, Annual Review of Biochemistry, August 2024 (jeon2024signalingfromras pages 4-6); Degirmenci et al., Cells, January 2020 (degirmenci2020targetingaberrantrasrafmekerk pages 3-5) |
| Catalytic reaction and substrate | ARAF catalyzes ATP-dependent transfer of phosphate to serine/threonine residues. Its best-established physiological substrates are MEK1/MAP2K1 and MEK2/MAP2K2, phosphorylated on their activation loops, thereby enabling MEK-dependent ERK1/2 activation. ARAF-associated MEK1 phosphorylation is lost or strongly reduced with kinase-dead ARAF variants. | RAF-family biochemical consensus plus ARAF immunoprecipitation kinase assays | Cook, 2024 (cook2024functionalassessmentof pages 27-31); Monaco et al., Clinical Cancer Research, December 2021 (monaco2021lxh254apotent pages 17-21) |
| Relative catalytic activity | Wild-type ARAF generally has the lowest basal and inducible MEK-kinase activity of the three RAF paralogs (BRAF > CRAF > ARAF), partly attributed to its noncanonical APE-region sequence. Low activity does not mean catalytically inactive: activated or mutant ARAF can robustly phosphorylate MEK. | Comparative biochemical and sequence evidence | Degirmenci et al., Cells, January 2020 (degirmenci2020targetingaberrantrasrafmekerk pages 3-5); Nelson et al., Blood, May 2014 (nelson2014somaticactivatingaraf pages 3-4) |
| Activation and localization | In the canonical model, inactive RAF is predominantly a cytosolic, 14-3-3-stabilized monomer. RAS-GTP recruits ARAF through CR1 to the plasma membrane; regulatory dephosphorylation and side-to-side RAF homo/heterodimerization promote kinase activation. ARAF Ser214 is the inhibitory CR2 14-3-3 site; dimerization and catalytic activity are experimentally required for strong ARAF-dependent MEK signaling in RAS-mutant models. | RAF-family structural mechanism with ARAF-specific mutagenesis | Jeon, Tkacik & Eck, August 2024 (jeon2024signalingfromras pages 4-6); Cook, 2024 (cook2024functionalassessmentof pages 27-31); Monaco et al., December 2021 (monaco2021lxh254apotent pages 17-21) |
| Mitochondrial MST2 role | ARAF also localizes to mitochondria in proliferating epithelial and tumor cells, where it binds and sequesters the pro-apoptotic kinase MST2/STK3. This anti-apoptotic function is substantially kinase-independent and changes with ARAF’s compartmental redistribution during epithelial differentiation. | Cell fractionation, microscopy, interaction, depletion, and differentiation studies | Rauch et al., Cell Death & Differentiation, 2016; summarized in ARAF-specific evidence (yang2026a‑rafaserinethreonine pages 5-6, yang2026a‑rafaserinethreonine pages 1-2) |
| Lung adenocarcinoma variant | Somatic ARAF p.S214C was identified in a stage-IV lung adenocarcinoma from a 66-year-old patient who had a near-complete response to sorafenib within two months and remained progression-free for five years. Tumor/normal sequencing showed 11/23 versus 0/18 variant reads and tumor RNA showed 48/56; engineered S214 ARAF mutants transformed human airway epithelial cells in a sorafenib-sensitive manner. Same-site ARAF and nearby RAF1 variants occurred in approximately 1% of an independent cohort. | Tumor/normal genome and transcriptome sequencing, cellular transformation assays, exceptional-responder observation | Imielinski et al., Journal of Clinical Investigation, April 2014 (imielinski2014oncogenicandsorafenibsensitive pages 1-2) |
| Langerhans-cell histiocytosis variant | One BRAF-wild-type LCH lesion carried same-allele somatic ARAF p.F351L plus p.Q347_A348del. The compound mutant strongly phosphorylated MEK and activated ERK, had activity only slightly below BRAF V600E, and produced 102.5 ± 8.5 soft-agar colonies per 4 cm² versus 0 ± 0 for wild-type ARAF; kinase-dead K336M abolished activity. | Purified lesional-cell sequencing, biochemical kinase assays, mutagenesis, and transformation assays | Nelson et al., Blood, May 15, 2014 (nelson2014somaticactivatingaraf pages 1-2, nelson2014somaticactivatingaraf pages 3-4, nelson2014somaticactivatingaraf pages 2-3) |
| LXH254 resistance | In five RAS-mutant cancer lines, ARAF loss increased sensitivity to the BRAF/CRAF-selective inhibitor LXH254 by 3–11-fold. Wild-type ARAF restored resistance, whereas kinase-dead K336M/D447A or dimer-deficient R362H did not. ARAF-only cells required >1,500 nM LXH254 for pathway inhibition versus <100 nM in BRAF- or CRAF-only cells. | CRISPR/isogenic-cell pharmacology, rescue experiments, kinase assays, and xenografts | Monaco et al., Clinical Cancer Research, December 2021 (monaco2021lxh254apotent pages 17-21, monaco2021lxh254apotent pages 21-24) |
| Live-cell ARAF engagement | Conditional NanoBRET assays showed that 13 type-II RAF inhibitors preferentially engaged BRAF over ARAF by 9–75-fold in KRAS-driven RAF complexes. LY3009120 and RAF709 had ARAF cellular IC50 values of 200 and 220 nM, whereas RAF265 and TAK-580 measured 6,400 and 4,000 nM. ARAF engagement—not merely BRAF/CRAF engagement—tracked with p-ERK suppression in tested KRAS-mutant cells. | Live-cell target-engagement and pathway pharmacology | Vasta et al., preprint October 2022; peer-reviewed Cell Chemical Biology, 2023 (vasta2022protomerselectivityof pages 6-9, vasta2022protomerselectivityof pages 9-11) |
Table: Concise evidence map for human ARAF/P10398, separating established molecular annotation from ARAF-specific experimental, disease, and pharmacological findings. Quantitative values are included where supported by the cited studies.
ARAF is one of the three mammalian RAF paralogs—ARAF, BRAF, and RAF1/CRAF—and belongs to the TKL branch of the protein-kinase superfamily. RAF-family architecture comprises three conserved regions: CR1, containing the RAS-binding domain and cysteine-rich/C1-like membrane-binding domain; CR2, a serine/threonine-rich regulatory segment with an inhibitory 14-3-3 site; and CR3, containing the catalytic protein-kinase domain, RAF dimer interface, and MEK-binding determinants. ARAF and CRAF lack the BRAF-specific N-terminal region, but otherwise share the core RAF regulatory organization (degirmenci2020targetingaberrantrasrafmekerk pages 3-5, jeon2024signalingfromras pages 4-6).
This architecture aligns with the user-supplied InterPro annotations: C1-like/DAG-phorbol-ester-binding folds correspond to the cysteine-rich portion of CR1, while the kinase-like and protein-kinase domains correspond to CR3. The C1-like annotation should not be interpreted to mean that ARAF functions principally as a conventional PKC-like DAG receptor; in RAF, this region contributes to RAS and membrane interactions within the larger regulatory apparatus.
The generic enzymatic reaction is:
ATP + protein serine/threonine-OH → ADP + phosphoprotein serine/threonine-O-phosphate.
The best-established physiologically relevant substrates are MEK1 and MEK2. Activated RAF phosphorylates their activation-loop serines, enabling MEK1/2 to phosphorylate ERK1/2. Contemporary RAF literature treats MEK1/2 as the principal, and often the only clearly established, physiological catalytic substrates of RAF proteins (cook2024functionalassessmentof pages 27-31).
ARAF-specific experiments support this assignment. Wild-type ARAF immunoprecipitates generated phosphorylated MEK1, whereas kinase-dead K336M and D447A proteins produced little or no p-MEK1. A dimer-deficient R362H protein also produced very little p-MEK1 and lacked associated BRAF/CRAF, demonstrating that productive ARAF signaling requires both an intact catalytic site and dimer assembly in those models (monaco2021lxh254apotent pages 17-21).
Wild-type ARAF generally has the lowest activity of the RAF paralogs—commonly ranked BRAF > CRAF > ARAF—in part because of sequence differences around its noncanonical APE-region motif. This is a relative statement, not evidence that ARAF is a pseudokinase: activated ARAF and oncogenic mutants can phosphorylate MEK strongly (degirmenci2020targetingaberrantrasrafmekerk pages 3-5, nelson2014somaticactivatingaraf pages 2-3).
Other reported ARAF substrates or outputs, such as SMAD2 linker phosphorylation, are substantially less established than MEK1/2 and appear context-dependent. They should not replace MEK1/2 in the primary annotation (yang2026a‑rafaserinethreonine pages 2-4).
The accepted RAF-family model—supported most extensively by recent BRAF/CRAF structures but applicable to conserved ARAF architecture—places inactive RAF in the cytosol as a compact, autoinhibited complex stabilized by 14-3-3. RAS-GTP binds the RAS-binding and cysteine-rich domains, recruits RAF to the inner plasma membrane, and promotes release of autoinhibition and side-to-side RAF dimerization (cook2024functionalassessmentof pages 27-31, jeon2024signalingfromras pages 4-6).
For ARAF, Ser214 is the inhibitory CR2 phosphorylation/14-3-3 site. Dephosphorylation of the homologous RAF regulatory site—mediated in the current family model by phosphatase machinery that includes the SHOC2–MRAS–PP1 complex—facilitates conversion to the active state. However, much of the highest-resolution SHOC2 and 14-3-3 structural work uses BRAF or CRAF; residue-level extrapolation beyond conserved ARAF Ser214 should therefore be regarded as family-based inference rather than direct ARAF structural observation (cook2024functionalassessmentof pages 27-31, jeon2024signalingfromras pages 4-6).
ARAF’s N-terminal acidic regulatory segment includes phosphorylation-sensitive residues around Ser299/Tyr301/Tyr302, and its activation loop includes Thr452/Thr455. Phosphorylation and dimerization cooperate to establish the active kinase conformation (cook2024functionalassessmentof pages 27-31, berlinska2025unravellingkrasbiology pages 10-13).
ARAF can form homodimers and heterodimers with BRAF or CRAF. In RAS-mutant cells, wild-type ARAF restored resistance to the BRAF/CRAF-biased inhibitor LXH254, whereas kinase-dead K336M/D447A and dimer-defective R362H did not. These rescue experiments provide unusually direct evidence that both catalytic activity and RAF heterodimerization are required for ARAF-dependent MAPK output in those settings (monaco2021lxh254apotent pages 17-21).
ARAF localization is dynamic rather than confined to one organelle:
The answer to “where does ARAF carry out its function?” is therefore function-specific: canonical MEK phosphorylation is chiefly associated with RAS-organized membrane signalosomes and RAF–MEK complexes, whereas the best-characterized kinase-independent anti-apoptotic activity occurs in cytoplasmic/mitochondrial compartments.
ARAF functions at the RAF/MAP3K tier of the pathway:
growth-factor receptor → RAS-GTP → ARAF-containing RAF dimer → MEK1/2 → ERK1/2 → context-dependent proliferation, differentiation, survival, and migration.
The 2024 Annual Review emphasizes that RAF operates not as a free binary switch but as an integrated regulatory assembly containing RAS, RAF dimers, MEK, 14-3-3, phosphatases, and chaperones. For ARAF, this framework explains how a comparatively weak isolated kinase can make substantial contributions in membrane-localized dimers and mutant-RAS signalosomes (jeon2024signalingfromras pages 4-6).
ARAF also binds and sequesters MST2/STK3, limiting MST2-dependent apoptotic signaling. During epithelial differentiation, redistribution of ARAF away from mitochondria changes access to MST2, linking intracellular location to cell fate. This activity is substantially kinase-independent and should be annotated as a scaffold/sequestration function rather than as phosphorylation of MST2 (yang2026a‑rafaserinethreonine pages 5-6, yang2026a‑rafaserinethreonine pages 1-2).
Older RAF literature also implicates ARAF in suppression of ASK1-dependent apoptosis, but the MST2 interaction has more precise ARAF-specific localization evidence. These noncanonical functions broaden ARAF biology without changing its primary enzymatic annotation.
The strongest exceptional-responder evidence comes from a 66-year-old woman with stage-IV lung adenocarcinoma. Oral sorafenib produced a near-complete radiographic response within two months, followed by approximately five years of progression-free, asymptomatic treatment. Tumor/normal whole-genome sequencing identified somatic ARAF p.S214C: 11/23 tumor-DNA reads versus 0/18 normal reads, with 48/56 tumor-RNA reads supporting expression. Engineered ARAF variants transformed immortalized human airway epithelial cells in a sorafenib-sensitive manner. Same-site ARAF variants and a nearby RAF1 variant collectively occurred in approximately 1% of an independent lung-adenocarcinoma cohort (Imielinski et al., published April 2014; https://doi.org/10.1172/JCI72763) (imielinski2014oncogenicandsorafenibsensitive pages 1-2).
This is compelling mechanistic and individual-patient evidence, but not a prospective biomarker trial. Sorafenib is multikinase-directed; therefore, the response cannot prove that isolated ARAF inhibition alone caused the clinical outcome.
In purified CD1a-positive lesional cells from a BRAF-wild-type LCH patient, Nelson et al. identified same-allele somatic ARAF p.F351L plus p.Q347_A348del. The compound mutant robustly phosphorylated MEK and activated ERK; its kinase activity was only slightly below BRAF V600E and was abolished by adding kinase-dead K336M. In soft agar it produced 102.5 ± 8.5 colonies per 4 cm², versus 0 ± 0 for wild-type ARAF after 22 days. Its in-vitro activity was inhibited by vemurafenib (published May 15, 2014; https://doi.org/10.1182/blood-2013-06-511139) (nelson2014somaticactivatingaraf pages 3-4, nelson2014somaticactivatingaraf pages 2-3).
The discovery cohort comprised exomes from three patients, followed by targeted testing of 52 LCH samples. Thus, the study establishes biological plausibility and oncogenicity but also demonstrates that activating ARAF lesions are uncommon relative to BRAF-driven LCH (nelson2014somaticactivatingaraf pages 1-2).
A recurrent ARAF mutation has been reported as a cause of central conducting lymphatic anomaly, with clinical responsiveness to a MEK inhibitor. The primary report appeared in Nature Medicine in 2019, volume 25, pages 1116–1122; DOI: https://doi.org/10.1038/s41591-019-0479-2 (yang2026a‑rafaserinethreonine pages 8-8). This is an important precision-medicine precedent because it targets the downstream MAPK output of activating ARAF rather than requiring an ARAF-selective drug. Detailed patient-level quantitative results were not available in the retrieved full text and are therefore not reproduced here.
Open Targets aggregates ARAF associations with cancer, hypertrophic cardiomyopathy, Noonan syndrome, Costello syndrome, and low-grade glioma. These scores are useful for hypothesis generation but should not be interpreted as equivalent to variant-level causal evidence; the same small literature set contributes to several disease labels (OpenTargets Search: -ARAF).
Two authoritative 2024 reviews consolidated a model in which RAF activation is governed by coordinated autoinhibition, membrane recruitment, regulatory-site dephosphorylation, 14-3-3 rearrangement, dimerization, and assembly with MEK. They also stress that the strongest structural data concern BRAF and CRAF; ARAF-specific structural coverage remains comparatively sparse (Jeon, Tkacik & Eck, August 2024, https://doi.org/10.1146/annurev-biochem-052521-040754; Spencer-Smith & Morrison, May 2024, https://doi.org/10.1042/BST20230552) (jeon2024signalingfromras pages 4-6, degirmenci2020targetingaberrantrasrafmekerk pages 3-5).
The 2023 peer-reviewed Cell Chemical Biology work, first available as a 2022 preprint, showed that inhibitor potency measured against isolated kinase domains can misrepresent engagement in intact RAS–RAF complexes. Across 13 type-II RAF inhibitors, live-cell BRAF-versus-ARAF engagement ratios ranged from 9- to 75-fold in KRAS-driven heterodimers. LY3009120 and RAF709 had ARAF cellular IC50 values of 200 and 220 nM, whereas RAF265 and TAK-580 were much weaker at 6,400 and 4,000 nM. ARAF engagement tracked p-ERK suppression in KRAS-mutant DLD-1 and MIA PaCa-2 cells, identifying insufficient ARAF occupancy as a potency-limiting property of nominally pan-RAF inhibitors (peer-reviewed DOI: https://doi.org/10.1016/j.chembiol.2023.07.019; preprint evidence retrieved at https://doi.org/10.21203/rs.3.rs-2175742/v1) (vasta2022protomerselectivityof pages 6-9, vasta2022protomerselectivityof pages 9-11).
This changes the therapeutic interpretation of ARAF: it is not merely the weakest RAF kinase but can be the least effectively drug-engaged protomer sustaining signaling in mutant-RAS complexes.
No ARAF-selective drug is currently established as an approved therapy, and the trial search did not identify a validated ARAF-genotype-specific interventional program. Present applications are instead:
In five RAS-mutant cancer lines, ARAF deletion increased LXH254 sensitivity 3–11-fold. In RAF-isogenic cells, BRAF- or CRAF-only signaling was inhibited below 100 nM LXH254, whereas ARAF-only cells required more than 1,500 nM; ARAF-knockout xenografts showed complete or near-complete regressions, although some later escaped through pathway reactivation or bypass. These are strong preclinical data, not proof of patient benefit (monaco2021lxh254apotent pages 17-21, monaco2021lxh254apotent pages 21-24).
The most defensible functional annotation is:
ARAF is a RAS-regulated RAF-family serine/threonine MAP3K whose primary catalytic substrates are MEK1/2. Its activity depends strongly on membrane recruitment, phosphorylation state, 14-3-3 remodeling, and RAF dimerization; it also executes kinase-independent mitochondrial/cytoplasmic anti-apoptotic functions through MST2 sequestration.
Three cautions are important. First, many regulatory details are inferred from the more extensively characterized BRAF and CRAF paralogs; they should be labeled RAF-family mechanisms unless directly tested in ARAF. Second, rare activating ARAF variants can be much more active than wild-type ARAF, so the phrase “weak kinase” does not predict mutant behavior. Third, therapeutic evidence is heterogeneous: the lung-cancer result is an exceptional case, CCLA supports downstream MEK inhibition, and inhibitor-engagement studies are primarily cellular or preclinical. None establishes a broadly validated, ARAF-selective standard of care.
References
(OpenTargets Search: -ARAF): Open Targets Query (-ARAF, 6 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(jeon2024signalingfromras pages 4-6): Hyesung Jeon, Emre Tkacik, and Michael J. Eck. Signaling from ras to raf: the molecules and their mechanisms. Aug 2024. URL: https://doi.org/10.1146/annurev-biochem-052521-040754, doi:10.1146/annurev-biochem-052521-040754. This article has 73 citations and is from a domain leading peer-reviewed journal.
(degirmenci2020targetingaberrantrasrafmekerk pages 3-5): Ufuk Degirmenci, Mei Wang, and Jiancheng Hu. Targeting aberrant ras/raf/mek/erk signaling for cancer therapy. Cells, 9:198, Jan 2020. URL: https://doi.org/10.3390/cells9010198, doi:10.3390/cells9010198. This article has 687 citations.
(cook2024functionalassessmentof pages 27-31): F Cook. Functional assessment of braf and craf through base editor 3 mutagenesis reveals residues and regions critical for erk1/2 signalling. Unknown journal, 2024.
(monaco2021lxh254apotent pages 17-21): Kelli-Ann Monaco, Scott Delach, Jing Yuan, Yuji Mishina, Paul Fordjour, Emma Labrot, Daniel McKay, Ribo Guo, Stacy Higgins, Hui Qin Wang, Jinsheng Liang, Karen Bui, John Green, Peter Aspesi, Jessi Ambrose, Felipa Mapa, Lesley Griner, Mariela Jaskelioff, John Fuller, Kenneth Crawford, Gwynn Pardee, Stephania Widger, Peter S. Hammerman, Jeffrey A. Engelman, Darrin D. Stuart, Vesselina G. Cooke, and Giordano Caponigro. Lxh254, a potent and selective araf-sparing inhibitor of braf and craf for the treatment of mapk-driven tumors. Clinical Cancer Research, 27:2061-2073, Dec 2021. URL: https://doi.org/10.1158/1078-0432.ccr-20-2563, doi:10.1158/1078-0432.ccr-20-2563. This article has 95 citations and is from a highest quality peer-reviewed journal.
(nelson2014somaticactivatingaraf pages 3-4): David S. Nelson, Willemijn Quispel, Gayane Badalian-Very, Astrid G. S. van Halteren, Cor van den Bos, Judith V. M. G. Bovée, Sara Y. Tian, Paul Van Hummelen, Matthew Ducar, Laura E. MacConaill, R. Maarten Egeler, and Barrett J. Rollins. Somatic activating araf mutations in langerhans cell histiocytosis. Blood, 123 20:3152-5, May 2014. URL: https://doi.org/10.1182/blood-2013-06-511139, doi:10.1182/blood-2013-06-511139. This article has 211 citations and is from a highest quality peer-reviewed journal.
(yang2026a‑rafaserinethreonine pages 5-6): Muhan Yang, Mengying Chen, Jinmei Wei, Yan-Ling Li, Chen Long, Yan Lei, and Yan-Hong Zhou. A‑raf: a serine/threonine protein kinase with important biological functions (review). Molecular Medicine Reports, 34:1-8, Jul 2026. URL: https://doi.org/10.3892/mmr.2026.13959, doi:10.3892/mmr.2026.13959. This article has 0 citations and is from a peer-reviewed journal.
(yang2026a‑rafaserinethreonine pages 1-2): Muhan Yang, Mengying Chen, Jinmei Wei, Yan-Ling Li, Chen Long, Yan Lei, and Yan-Hong Zhou. A‑raf: a serine/threonine protein kinase with important biological functions (review). Molecular Medicine Reports, 34:1-8, Jul 2026. URL: https://doi.org/10.3892/mmr.2026.13959, doi:10.3892/mmr.2026.13959. This article has 0 citations and is from a peer-reviewed journal.
(imielinski2014oncogenicandsorafenibsensitive pages 1-2): Marcin Imielinski, Heidi Greulich, Bethany Kaplan, Luiz Araujo, Joseph Amann, Leora Horn, Joan Schiller, Miguel A. Villalona-Calero, Matthew Meyerson, and David P. Carbone. Oncogenic and sorafenib-sensitive araf mutations in lung adenocarcinoma. The Journal of clinical investigation, 124 4:1582-6, Apr 2014. URL: https://doi.org/10.1172/jci72763, doi:10.1172/jci72763. This article has 144 citations.
(nelson2014somaticactivatingaraf pages 1-2): David S. Nelson, Willemijn Quispel, Gayane Badalian-Very, Astrid G. S. van Halteren, Cor van den Bos, Judith V. M. G. Bovée, Sara Y. Tian, Paul Van Hummelen, Matthew Ducar, Laura E. MacConaill, R. Maarten Egeler, and Barrett J. Rollins. Somatic activating araf mutations in langerhans cell histiocytosis. Blood, 123 20:3152-5, May 2014. URL: https://doi.org/10.1182/blood-2013-06-511139, doi:10.1182/blood-2013-06-511139. This article has 211 citations and is from a highest quality peer-reviewed journal.
(nelson2014somaticactivatingaraf pages 2-3): David S. Nelson, Willemijn Quispel, Gayane Badalian-Very, Astrid G. S. van Halteren, Cor van den Bos, Judith V. M. G. Bovée, Sara Y. Tian, Paul Van Hummelen, Matthew Ducar, Laura E. MacConaill, R. Maarten Egeler, and Barrett J. Rollins. Somatic activating araf mutations in langerhans cell histiocytosis. Blood, 123 20:3152-5, May 2014. URL: https://doi.org/10.1182/blood-2013-06-511139, doi:10.1182/blood-2013-06-511139. This article has 211 citations and is from a highest quality peer-reviewed journal.
(monaco2021lxh254apotent pages 21-24): Kelli-Ann Monaco, Scott Delach, Jing Yuan, Yuji Mishina, Paul Fordjour, Emma Labrot, Daniel McKay, Ribo Guo, Stacy Higgins, Hui Qin Wang, Jinsheng Liang, Karen Bui, John Green, Peter Aspesi, Jessi Ambrose, Felipa Mapa, Lesley Griner, Mariela Jaskelioff, John Fuller, Kenneth Crawford, Gwynn Pardee, Stephania Widger, Peter S. Hammerman, Jeffrey A. Engelman, Darrin D. Stuart, Vesselina G. Cooke, and Giordano Caponigro. Lxh254, a potent and selective araf-sparing inhibitor of braf and craf for the treatment of mapk-driven tumors. Clinical Cancer Research, 27:2061-2073, Dec 2021. URL: https://doi.org/10.1158/1078-0432.ccr-20-2563, doi:10.1158/1078-0432.ccr-20-2563. This article has 95 citations and is from a highest quality peer-reviewed journal.
(vasta2022protomerselectivityof pages 6-9): James Vasta, Ani Michaud, Chad Zimprich, Morgan Thomas, Jennifer Wilkinson, J. Aaron Crapster, and Matthew Robers. Protomer selectivity of raf inhibitors within the ras/raf signalosome. Unknown journal, Oct 2022. URL: https://doi.org/10.21203/rs.3.rs-2175742/v1, doi:10.21203/rs.3.rs-2175742/v1.
(vasta2022protomerselectivityof pages 9-11): James Vasta, Ani Michaud, Chad Zimprich, Morgan Thomas, Jennifer Wilkinson, J. Aaron Crapster, and Matthew Robers. Protomer selectivity of raf inhibitors within the ras/raf signalosome. Unknown journal, Oct 2022. URL: https://doi.org/10.21203/rs.3.rs-2175742/v1, doi:10.21203/rs.3.rs-2175742/v1.
(yang2026a‑rafaserinethreonine pages 2-4): Muhan Yang, Mengying Chen, Jinmei Wei, Yan-Ling Li, Chen Long, Yan Lei, and Yan-Hong Zhou. A‑raf: a serine/threonine protein kinase with important biological functions (review). Molecular Medicine Reports, 34:1-8, Jul 2026. URL: https://doi.org/10.3892/mmr.2026.13959, doi:10.3892/mmr.2026.13959. This article has 0 citations and is from a peer-reviewed journal.
(berlinska2025unravellingkrasbiology pages 10-13): E Berlinska. Unravelling kras biology: characterization of the kras-raf signalosome and its functional dynamics at the cell membrane. Unknown journal, 2025.
(yang2026a‑rafaserinethreonine pages 8-8): Muhan Yang, Mengying Chen, Jinmei Wei, Yan-Ling Li, Chen Long, Yan Lei, and Yan-Hong Zhou. A‑raf: a serine/threonine protein kinase with important biological functions (review). Molecular Medicine Reports, 34:1-8, Jul 2026. URL: https://doi.org/10.3892/mmr.2026.13959, doi:10.3892/mmr.2026.13959. This article has 0 citations and is from a peer-reviewed journal.