MAPK Signaling
Phosphorylation is the reversible process of attaching a phosphate group to a specific amino-acid residue on a protein. Functionally, phosphorylation acts as a simple molecular switch that can activate, deactivate, or modulate the function of a protein. Addition and removal of phosphate groups provide spatial and temporal control over protein activity. Phosphorylation is tightly controlled by a competing interdependent network of kinases - which donate phosphate groups to a substrate protein, and phosphorylases - which remove them from a substrate.
Mitogen-activated protein kinases (MAPKs) are a highly conserved and ubiquitously expressed family of enzymatic kinases that phosphorylate many different target substrates. MAP-kinases are part of a larger, tiered phosphorylation cascade that includes MAP2Ks and MAP3Ks. This tiered organization affords flexibility, allowing a broad range of higher-order kinases to respond to stimuli and control cellular function through activation of a smaller subset of MAP-kinases that interact directly with other functional proteins.
MAP-kinases play a major role in nearly every cellular process. MAPK dependent phosphorylation is implicated in signaling cascades that regulate cell-cycle progression, differentiation, development, and apoptosis.
(Additional Reading: Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH (April 2001). "Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions". Endocr. Rev. 22 (2): 153–83.)
MAPK
p38 (MAP kinase p38):
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases 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. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires...
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MAPK1 - ERK2
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 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. The activation of this kinase requires its...
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| MAPK10 (Mitogen-Activated Protein Kinase 10): | MAPK10 antibodies | MAPK10 Proteins | |
| MAPK11 (Mitogen-Activated Protein Kinase 11): | MAPK11 antibodies | MAPK11 Proteins | |
| MAPK12 (Mitogen-Activated Protein Kinase 12): | MAPK12 antibodies | MAPK12 ELISA Kits | MAPK12 Proteins |
| MAPK13 (Mitogen-Activated Protein Kinase 13): | MAPK13 antibodies | MAPK13 ELISA Kits | MAPK13 Proteins |
| MAPK14 (Mitogen-Activated Protein Kinase 14): | MAPK14 antibodies | MAPK14 ELISA Kits | MAPK14 Proteins |
| MAPK3 (Mitogen-Activated Protein Kinase 3): | MAPK3 antibodies | MAPK3 ELISA Kits | MAPK3 Proteins |
| MAPK4 (Mitogen-Activated Protein Kinase 4): | MAPK4 antibodies | MAPK4 Proteins | |
| MAPK6 (Mitogen-Activated Protein Kinase 6): | MAPK6 antibodies | MAPK6 ELISA Kits | MAPK6 Proteins |
| MAPK7 (Mitogen-Activated Protein Kinase 7): | MAPK7 antibodies | MAPK7 Proteins | |
| MAPK8 - JNK: | MAPK8 antibodies | MAPK8 ELISA Kits | MAPK8 Proteins |
| MAPK9 (Mitogen-Activated Protein Kinase 9): | MAPK9 antibodies | MAPK9 ELISA Kits | MAPK9 Proteins |
MAP2K
MAP2K1 (Mitogen-Activated Protein Kinase Kinase 1):
The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon...
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MAP2K2 (Mitogen-Activated Protein Kinase Kinase 2):
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...
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| MAP2K3 (Mitogen-Activated Protein Kinase Kinase 3): | MAP2K3 antibodies | MAP2K3 ELISA Kits | MAP2K3 Proteins |
| MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4): | MAP2K4 antibodies | MAP2K4 ELISA Kits | MAP2K4 Proteins |
| MAP2K5 (Mitogen-Activated Protein Kinase Kinase 5): | MAP2K5 antibodies | MAP2K5 ELISA Kits | MAP2K5 Proteins |
| MAP2K6 (Mitogen-Activated Protein Kinase Kinase 6): | MAP2K6 antibodies | MAP2K6 ELISA Kits | MAP2K6 Proteins |
| MAP2K7 (Mitogen-Activated Protein Kinase Kinase 7): | MAP2K7 antibodies | MAP2K7 ELISA Kits | MAP2K7 Proteins |
MAP3K
MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1):
The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in...
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MAP3K11 (Mitogen-Activated Protein Kinase Kinase Kinase 11):
The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates IkappaB kinase alpha and beta, and is found to be involved in the...
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| MAP3K12 (Mitogen-Activated Protein Kinase Kinase Kinase 12): | MAP3K12 antibodies | MAP3K12 Proteins | |
| MAP3K2 (Mitogen-Activated Protein Kinase Kinase Kinase 2): | MAP3K2 antibodies | MAP3K2 Proteins | |
| MAP3K3 (Mitogen-Activated Protein Kinase Kinase Kinase 3): | MAP3K3 antibodies | MAP3K3 Proteins | |
| MAP3K4 (Mitogen-Activated Protein Kinase Kinase Kinase 4): | MAP3K4 antibodies | MAP3K4 Proteins | |
| MAP3K5 (Mitogen-Activated Protein Kinase Kinase Kinase 5): | MAP3K5 antibodies | MAP3K5 ELISA Kits | MAP3K5 Proteins |
| ARAF (V-Raf Murine Sarcoma 3611 Viral Oncogene Homolog): | ARAF antibodies | ARAF ELISA Kits | ARAF Proteins |
| BRAF (V-Raf Murine Sarcoma Viral Oncogene Homolog B1): | BRAF antibodies | BRAF ELISA Kits | BRAF Proteins |
| RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1): | RAF1 antibodies | RAF1 ELISA Kits | RAF1 Proteins |
RAF
ARAF (V-Raf Murine Sarcoma 3611 Viral Oncogene Homolog):
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.[provided by RefSeq, Jan 2012].
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BRAF (V-Raf Murine Sarcoma Viral Oncogene Homolog B1):
This gene encodes a protein belonging to the raf/mil family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERKs signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene are associated with cardiofaciocutaneous syndrome, a disease characterized by heart defects, mental retardation and a distinctive facial...
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| RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1): | RAF1 antibodies | RAF1 ELISA Kits | RAF1 Proteins |
RAS
NRAS - GTPase NRas
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...
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HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog):
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...
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Activators
CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)):
The protein encoded by this gene is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression. This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The product of oncogene Dbl was reported to...
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PAK1 (P21-Activated Kinase 1):
This gene encodes a family member of serine/threonine p21-activating kinases, known as PAK proteins. These proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling, and they serve as targets for the small GTP binding proteins Cdc42 and Rac. This specific family member regulates cell motility and morphology. Alternatively spliced transcript...
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| GCK (Glucokinase (Hexokinase 4)): | GCK antibodies | GCK ELISA Kits | GCK Proteins |
| NRAS - GTPase NRas: | NRAS antibodies | NRAS ELISA Kits | NRAS Proteins |
| MAP4K3 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 3): | MAP4K3 antibodies | MAP4K3 Proteins | |
| PAK2 (P21-Activated Kinase 2): | PAK2 antibodies | PAK2 ELISA Kits | PAK2 Proteins |
| HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog): | HRAS antibodies | HRAS ELISA Kits | HRAS Proteins |
Targets
ATF2 (Activating Transcription Factor 2):
This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. It forms a homodimer or a heterodimer with c-Jun and stimulates CRE-dependent transcription. This protein is also a histone acetyltransferase (HAT) that specifically acetylates histones H2B and H4 in...
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BCL2 (B-Cell CLL/lymphoma 2):
This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Two transcript variants, produced by alternate splicing, differ in their C-terminal ends. [provided by...
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BAD (BCL2-Associated Agonist of Cell Death):
The protein encoded by this gene is a member of the BCL-2 family. BCL-2 family members are known to be regulators of programmed cell death. This protein positively regulates cell apoptosis by forming heterodimers with BCL-xL and BCL-2, and reversing their death repressor activity. Proapoptotic activity of this protein is regulated through its phosphorylation. Protein kinases AKT and MAP kinase,...
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BTG2 (BTG Family, Member 2):
The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein is involved in the regulation of the G1/S transition of the cell cycle. [provided by RefSeq, Jul 2008].
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CANX - Calnexin
This gene encodes a member of the calnexin family of molecular chaperones. The encoded protein is a calcium-binding, endoplasmic reticulum (ER)-associated protein that interacts transiently with newly synthesized N-linked glycoproteins, facilitating protein folding and assembly. It may also play a central role in the quality control of protein folding by retaining incorrectly folded protein...
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CASP9 - Caspase 9
This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed...
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