Phospho-RAF1 (S43) Antibody

Phospho-RAF1 (Ser43) antibody targets the phosphorylated form of RAF1, a serine/threonine-protein kinase crucial in mediating signaling between membrane-bound Ras GTPases and the MAPK/ERK cascade. This pivotal role regulates critical cell fate decisions, encompassing proliferation, differentiation, apoptosis, survival, and oncogenic transformation. RAF1 activation initiates a MAPK cascade involving sequential phosphorylation of MAP2K1/MEK1, MAP2K2/MEK2, MAPK3/ERK1, and MAPK1/ERK2. Phosphorylated RAF1 (Ser338 and Ser339, by PAK1) further phosphorylates BAD (Ser75), influencing apoptosis. Additional targets include adenylyl cyclases ADCY2, ADCY5, and ADCY6 (resulting in activation), PPP1R12A (resulting in phosphatase inhibition), and TNNT2 (cardiac muscle troponin T). RAF1 modulates NF-κB activation and inhibits signaling molecules involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation, and angiogenesis (RB1). Its mitochondrial translocation, binding to BCL2, and displacement of BAD also contribute to apoptosis regulation. Furthermore, RAF1 regulates Rho signaling and migration, impacting wound healing. In epithelial cells, RAF1 can contribute to oncogenic transformation by repressing the tight junction protein occludin (OCLN) through SNAI2/SLUG upregulation. Finally, RAF1 restricts caspase activation in response to stimuli such as Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation.

Numerous studies highlight the diverse roles and clinical significance of RAF1:

• RAF1 and RIT1 variants have been functionally assessed for pathogenicity. PMID: 29402968
• A familial case of Noonan syndrome linked to a germline RAF1 p.S427G substitution showed no increased cancer risk, contrasting with somatic RAF1 mutations observed in various cancers. PMID: 30204961
• RAF1 acts as a negative regulator in hepatocarcinogenesis. PMID: 28000790
• A case of inherited RAF1-associated Noonan syndrome presented with antenatal skull abnormalities, subdural hematomas, delayed myelination, and polymicrogyria. PMID: 27753652
• RAF1 is a potential prognostic factor and therapeutic target in non-small cell lung cancer (NSCLC). PMID: 29484414
• RAF1 binding to SPRY4 is regulated by miR-1908 in gliomas. PMID: 29048686
• High RAF1 expression correlates with malignant melanoma. PMID: 28677804
• RAF1 variants in the CR2 domain have been associated with biventricular hypertrophy in premature neonates. PMID: 28777121
• CNK1 regulates RAF and AKT signaling and influences cell fate decisions. PMID: 27901111
• CRAF is an alternative oncogene in BRAF/NRAS/GNAQ/GNA11 wild-type melanomas. PMID: 27273450
• miR-125a acts as a tumor suppressor by downregulating RAF1. PMID: 28445974
• ciRS-7 overexpression inhibits miR-7, leading to RAF1 oncogene activation. PMID: 28174233
• miR-497 targets RAF1 and may serve as a tumor suppressor and diagnostic marker in gastric cancer. PMID: 28586056
• RAF1's role in hepatocellular carcinoma survival and the potential use of sorafenib as an adjuvant therapy are under investigation. PMID: 26981887
• Mutational activation of Kit, Ras/Raf/Erk, and Akt pathways highlights their importance as therapeutic targets. PMID: 27391150
• Des-gamma-carboxy prothrombin (DCP) antagonizes sorafenib's inhibitory effects on hepatocellular carcinoma (HCC) by activating Raf/MEK/ERK and PI3K/Akt/mTOR pathways. PMID: 27167344
• DiRas3 binds to KSR1 independently of its interaction with activated Ras and RAF. PMID: 27368419
• The RhoA/ROCK and Raf-1/CK2 pathways mediate TNF-α-induced endothelial cytotoxicity. PMID: 28743511
• Abnormal Raf-1 kinase feedback regulation can enhance its anti-apoptotic function, even without gene mutation, making it a potential drug target to enhance chemotherapy or radiotherapy sensitivity. PMID: 27841865
• RAF1 maintains the transformed phenotype of colorectal cancer (CRC) cells, including those with mutated KRAS. PMID: 27670374
• Hsp90's role in CRAF maturation and activation is a limiting factor in maintaining its function. PMID: 27703006
• Oncogenic NFIA:RAF1 fusion activation of the MAPK pathway is associated with pilocytic astrocytoma. PMID: 27810072
• IGF2BP2 interferes with Raf-1 degradation, contributing to colorectal carcinogenesis. PMID: 27153315
• miR-125b overexpression reduces RAF1 expression, promoting macrophage apoptosis. PMID: 27363278
• Griffipavixanthone (GPX) inhibits B-RAF and C-RAF in esophageal cancer cells. PMID: 26646323
• RAF1 upregulation is associated with triple-negative breast cancer. PMID: 26513016
• Structural insights into C-Raf C-terminal phosphopeptide interaction with 14-3-3zeta protein are available. PMID: 26295714
• CD166 regulates MCAM via PI3K/AKT and c-Raf/MEK/ERK signaling, potentially inhibiting MCAM ubiquitin E3 ligases. PMID: 26004137
• A kinase module involving c-Raf/PI3K/Lyn and Fgr functions in retinoic acid-induced maturation of leukemia cells. PMID: 25817574
• Abnormal Ras/MAPK pathway activation may contribute to pulmonary vascular disease in Noonan syndrome patients with specific RAF1 mutations. PMID: 25706034
• RAF1 may be a prognostic biomarker in chordoma. PMID: 25755752
• Structural insights into RasQ61L mutant interaction with Raf-1 are available. PMID: 25684575
• pDAPK(S308) may serve as a predictive biomarker for Raf inhibitor combination therapy. PMID: 26100670
• DJ-1 stimulates c-Raf self-phosphorylation and subsequent MEK/ERK1/2 phosphorylation. PMID: 26048984
• Truncated RAF1 and BRAF proteins can confer resistance to RTK-targeted therapy in cancer cells. PMID: 25473895
• miR-455-RAF1 may be a therapeutic target for colorectal carcinoma. PMID: 25355599
• Overexpression of several genes, including RAF1, can compensate for EGFR in EGFR-dependent cells. PMID: 25512530
• Aberrant expression of A-, B-, and C-RAF, and COT is frequent in papillary thyroid carcinoma (PTC), with COT overexpression correlating with recurrence. PMID: 25674762
• Structural details of human Raf1 kinase N-terminus binding to human RKIP are available. PMID: 24863296
• RAF1 is implicated in apoptosis regulation along with anti-apoptotic Bcl-2 family members. PMID: 24969872
• miR-7-5p functions as a tumor suppressor by targeting RAF1 in glioblastoma microvascular endothelial cells. PMID: 25027403
• High CAV-1 expression disrupts BRaf/CRaf heterodimers, inhibiting MAPK pathway activation during dasatinib treatment. PMID: 24486585
• Shoc2 and HUWE1 regulate RAF-1 ubiquitination and levels. PMID: 25022756
• The Raf-1/JNK/p53/p21 pathway and NFκB1 are implicated in apoptosis regulation. PMID: 22282237
• Higher RAF1 mRNA expression and AKT/ERK activation may confer vinorelbine resistance in non-small cell lung cancer. PMID: 24427333
• RAF1 mutations have been analyzed in childhood-onset dilated cardiomyopathy. PMID: 24777450
• miR-195 expression or Raf-1 knockdown reduces tumor cell survival. PMID: 23760062
• SRC, RAF1, and PTK2B genes may play roles in neurotransmission and central nervous system signaling. PMID: 24108181
• C-RAF mutations confer resistance to melanoma cell lines. PMID: 23737487
• ARAF stabilizes BRAF:CRAF complexes during RAF inhibitor treatment, subtly regulating signaling. PMID: 22926515

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HGNC: 9829

OMIM: 164760

KEGG: hsa:5894

STRING: 9606.ENSP00000251849

UniGene: Hs.159130