Ras-MAPK Pathway
Representative Targets in RAS-MAPK Pathway Full List of Targets in RAS-MAPK Pathway Tested Data-Supported Products for Targeting RAS-MAPK Pathway
The Ras-mitogen-activated protein kinase (MAPK) pathway, consisting of the Ras-Raf-MEK-ERK signaling cascade, regulates a multitude of cellular processes, including growth, differentiation, and apoptosis. This pathway, which transmits signals from the cell membrane to the nucleus, involves a series of phosphorylation events initiated by the binding of growth factors to cell surface receptors. Once activated, RAS, a small GTPase, serves as a critical molecular switch that triggers the activation of RAF, MEK, and ultimately MAPK, leading to the transcription of genes that dictate cell fate. The importance of the RAS-MAPK pathway is underscored by its tight regulation and the severe consequences of its dysregulation. Mutations and alterations within components of this pathway are implicated in the pathogenesis of a wide array of diseases, most notably cancer, where aberrant signaling can lead to uncontrolled cell proliferation and survival. Furthermore, its role is not limited to oncogenesis; abnormalities in the RAS-MAPK pathway have also been associated with developmental disorders and neurodegenerative diseases.
Figure 1 The RAS-MAPK cascade. (Dillon, 2021)
Representative Targets in RAS-MAPK Pathway
MAPK3
Protein Kinase C alpha (PRKCA) is a pivotal enzyme in the classical Protein Kinase C (PKC) family, which plays a critical role in the transduction of signals received at the cell surface into cellular responses. PRKCA is activated by the binding of diacylglycerol (DAG) and calcium ions, subsequently translocating from the cytosol to the plasma membrane where it becomes active. Once activated, PRKCA influences several pathways that govern cellular life and death decisions, demonstrating its importance in maintaining cellular homeostasis. Its roles extend to the regulation of gene expression, modulation of membrane receptor function, and the activation of other enzymes that are crucial in metabolic pathways. Importantly, PRKCA has been implicated in the pathogenesis of various diseases, including cancer, cardiovascular diseases, and neurological disorders, highlighting its significance not only in normal cellular physiology but also in disease states.
Recommended Mouse Anti-MAPK3 mAb (CAT#: ZG-0022C)
Figure 2 Mouse Anti-MAPK3 Antibody (clone 1C11) in IHC. Immunohistochemical analysis of paraffin-embedded Human Breast Carcinoma Tissue using ERK1 Mouse mAb diluted at 1:200.
Recommended Mouse Anti-MAPK3 mAb (CAT#: ZG-0023C)
Figure 3 Mouse Anti-MAPK3 Antibody (clone 4G11) in IHC. Immunohistochemical analysis of paraffin-embedded Human Breast Carcinoma Tissue using ERK1 Mouse mAb diluted at 1:200.
Recommended Mouse Anti-MAPK3 mAb (CAT#: ZG-0024C)
Figure 4 Mouse Anti-MAPK3 Antibody (clone 5E9) in IHC. Immunohistochemical analysis of paraffin-embedded Human-uterus tissue.1, ERK1 Mouse Monoclonal Antibody (5E9) was diluted at 1:200 (4°C, overnight). 2, Sodium citrate pH 6.0 was used for Antibody retrieval (>98°C, 20min). 3, Secondary antibody was diluted at 1:200 (room temperature, 30 min). Negative control was used by Secondary antibody only.
BRAF
The BRAF gene, an integral component of the mitogen-activated protein kinase (MAPK) signaling pathway, plays a pivotal role in regulating cell growth, proliferation, and differentiation. Mutations in the BRAF gene have been extensively studied in various cancers, including ovarian cancer, where they contribute to the dysregulation of cellular processes leading to oncogenesis. In ovarian cancer, BRAF mutations have been identified as key drivers of tumorigenesis, impacting disease progression and therapeutic outcomes. The most common mutation, BRAF V600E, results in constitutive activation of the MAPK pathway, leading to uncontrolled cell proliferation and evasion of apoptosis. Understanding the biology of BRAF in ovarian cancer is crucial for developing targeted therapies that specifically inhibit aberrant BRAF signaling, thereby offering potential avenues for personalized treatment strategies.
Recommended Mouse Anti-BRAF mAb (CAT#: ZG-053R)
Figure 5 Mouse Anti-BRAF Antibody (ZG-053R) in IHC. Immunohistochemistry analysis of paraffin-embedded human bladder carcinoma tissue (left) and lung carcinoma tissue (right) showing cytoplasmic localization with DAB staining using Raf-B monoclonal antibody.
Recommended Rabbit Anti-BRAF mAb (CAT#: ZG-0572J)
Figure 6 Rabbit Anti-BRAF Antibody (ZG-0572J) in IHC. IHC image of ZG-0572J diluted at 1:100 and staining in paraffin-embedded human testis tissue performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4°C overnight. The primary is detected by a Goat anti-rabbit IgG polymer labeled by HRP and visualized using 0.05% DAB.
Recommended Rabbit Anti-BRAF mAb (CAT#: ZG-0299U)
Figure 7 Rabbit Anti-BRAF Antibody (ZG-0299U) in IHC-P. Formalin fixed, paraffin embedded human tissues (4 μm sections) stained with Anti - B-raf antibody. Nuclear B-raf expression in the epithelium and stromal cells in normal bowel mucosa tissue.
RAF1
RAF1, also known as c-Raf, is a crucial serine/threonine kinase within the MAPK/ERK signaling pathway, a key regulator of cell division, differentiation, and survival. As a part of the Ras-Raf-MEK-ERK cascade, RAF1 is activated by the binding of Ras to its domain, leading to a series of phosphorylation events that ultimately promote cellular proliferation and prevent apoptosis. Its importance is underscored by its involvement in various physiological processes and its implication in pathological conditions, including cancer. Mutations or dysregulations in RAF1 have been associated with a spectrum of human diseases, notably Noonan syndrome and various types of carcinomas, highlighting its role as a proto-oncogene. Furthermore, RAF1 interacts with other cellular pathways, indicating its multifaceted role in regulating cell fate decisions. This complexity not only underscores the biological significance of RAF1 but also presents challenges in targeting it for therapeutic purposes.
Recommended Rabbit Anti-RAF1 mAb (CAT#: ZG-0539U)
Figure 8 Rabbit Anti-Phospho-RAF1 (S621) Antibody (ZG-0539U) in IF. Immunofluorescence staining of HepG2 cells(treated with 50mM Calyculin A for 30min) with ZG-0539U at 1:100, counter-stained with DAPI. The cells were fixed in 4% formaldehyde, permeabilized using 0.2% Triton X-100 and blocked in 10% normal Goat Serum. The cells were then incubated with the antibody overnight at 4°C. The secondary antibody was Alexa Fluor 488-congugated Goat Anti-Rabbit IgG (H+L).
Recommended Rabbit Anti-RAF1 mAb (CAT#: ZG-0540U)
Figure 9 Rabbit Anti-Phospho-RAF1 (S259) Antibody (ZG-0540U) in IHC. IHC image of ZG-0540U diluted at 1:100 and staining in paraffin-embedded human endometrial cancer performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4°C overnight. The primary is detected by a biotinylated secondary antibody and visualized using an HRP conjugated SP system.
Full List of Targets in RAS-MAPK Pathway
| Biomarker | Alternative Names | Gene ID | UniProt ID | Roles |
| ARAF | PKS2; A-RAF; ARAF1; RAFA1 | 369 | P10398 | This proto-oncogene belongs to the RAF subfamily of the Ser/Thr protein kinase family, and maybe involved in cell growth and development. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. |
| BRAF | B-Raf Proto-Oncogene, Serine/Threonine Kinase; V-Raf Murine Sarcoma Viral Oncogene Homolog B1; V-Raf Murine Sarcoma Viral Oncogene Homolog B; Proto-Oncogene B-Raf; BRAF1; RAFB1; B-Raf Proto-Oncogene Serine/Threonine-Protein Kinase (P94); Murine Sarcoma Viral (V-Raf) Oncogene Homolog B1; Serine/Threonine-Protein Kinase B-Raf | 673 | P15056 | This gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene, most commonly the V600E mutation, are the most frequently identified cancer-causing mutations in melanoma, and have been identified in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of lung. Mutations in this gene are also associated with cardiofaciocutaneous, Noonan, and Costello syndromes, which exhibit overlapping phenotypes. A pseudogene of this gene has been identified on the X chromosome. |
| HRAS | HRAS; Harvey rat sarcoma viral oncogene homolog; CTLO; HAMSV; HRAS1; RASH1; p21ras; C-H-RAS; H-RASIDX; C-BAS/HAS; C-HA-RAS1; GTPase HRas; p19 H-RasIDX protein; c-has/bas p21 protein; transforming protein p21; Ha-Ras1 proto-oncoprotein; c-ras-Ki-2 activated oncogene; GTP- and GDP-binding peptide B; transformation gene: oncogene HAMSV; Harvey rat sarcoma viral oncoprotein; Ras family small GTP binding protein H-Ras; v-Ha-ras Harvey rat sarcoma viral oncogene homolog | 3265 | P01112 | This gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. Mutations in this gene cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, mental retardation, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Defects in this gene are implicated in a variety of cancers, including bladder cancer, follicular thyroid cancer, and oral squamous cell carcinoma. Multiple transcript variants, which encode different isoforms, have been identified for this gene. [provided by RefSeq, Jul 2008] |
| KRAS | NS; NS3; CFC2; RALD; K-Ras; KRAS1; KRAS2; RASK2; KI-RAS; C-K-RAS; K-RAS2A; K-RAS2B; K-RAS4A; K-RAS4B; c-Ki-ras2 | 3845 | P01116 | This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008] |
| MAP2K2 | CFC4; MEK2; MKK2; MAPKK2; PRKMK2 | 5605 | P36507 | The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. |
| MAPK1 | ERK; p38; p40; p41; ERK2; ERT1; NS13; ERK-2; MAPK2; PRKM1; PRKM2; P42MAPK; p41mapk; p42-MAPK | 5594 | P28482 | This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. |
| MAPK3 | Mitogen-Activated Protein Kinase 3; Extracellular Signal-Regulated Kinase 1; Microtubule-Associated Protein 2 Kinase; Insulin-Stimulated MAP2 Kinase; MAP Kinase Isoform P44; EC 2.7.11.24; P44-ERK1; P44-MAPK; PRKM3; ERK-1; ERK1 | 5595 | P27361 | The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008] |
| NRAS | NRAS Proto-Oncogene, GTPase; Neuroblastoma RAS Viral (V-Ras) Oncogene Homolog; Neuroblastoma RAS Viral Oncogene Homolog; Transforming Protein N-Ras; V-Ras Neuroblastoma RAS Viral Oncogene Homolog; N-Ras Protein Part 4; GTPase NRas; HRAS1 | 4893 | P01111 | This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. [provided by RefSeq, Jun 2011] |
| RAF1 | Raf-1 Proto-Oncogene, Serine/Threonine Kinase; V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1; C-Raf Proto-Oncogene, Serine/Threonine Kinase; Proto-Oncogene C-RAF; EC 2.7.11.1; Raf-1; CRAF; V-Raf-1 Murine Leukemia Viral Oncogene-Like Protein 1; RAF Proto-Oncogene Serine/Threonine-Protein Kinase | 5894 | P04049 | This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. [provided by RefSeq, Jul 2008] |
Tested Data-Supported Products for Targeting RAS-MAPK Pathway
Reference
- Dillon, Martha, et al. "Progress on Ras/MAPK signaling research and targeting in blood and solid cancers." Cancers 13.20 (2021): 5059.
For research use only. Not intended for any clinical use.
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