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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

MAPK14 (Mitogen-Activated Protein Kinase 14):

Western blot analysis of extracts from NIH-3T3 (Line 1, 4, 7 and 10) and COS7 (Line 2, 5, 8 and 11 and K562 (Line 3, 6, 9 and 12) cells, untreated or treated with

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... More...

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... More...

MAPK10 (Mitogen-Activated Protein Kinase 10):

MAPK11 (Mitogen-Activated Protein Kinase 11):

MAPK12 (Mitogen-Activated Protein Kinase 12):

MAPK13 (Mitogen-Activated Protein Kinase 13):

MAPK14 (Mitogen-Activated Protein Kinase 14):

MAPK3 (Mitogen-Activated Protein Kinase 3):

MAPK4 (Mitogen-Activated Protein Kinase 4):

MAPK6 (Mitogen-Activated Protein Kinase 6):

MAPK7 (Mitogen-Activated Protein Kinase 7):

MAPK8 - JNK:

MAPK9 (Mitogen-Activated Protein Kinase 9):

MAP2K

MAP2K1 (Mitogen-Activated Protein Kinase Kinase 1):

Immunohistochemical analysis of paraffin-embedded human breast carcinoma tissue using MEK1 (Ab-291) antibody (E021286).

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... More...

MAP2K2 (Mitogen-Activated Protein Kinase Kinase 2):

Immunohistochemical analysis of paraffin-embedded human breast carcinoma tissue using MEK2 (Ab-394) antibody (E021008).

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... More...

MAP2K3 (Mitogen-Activated Protein Kinase Kinase 3):

MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4):

MAP2K5 (Mitogen-Activated Protein Kinase Kinase 5):

MAP2K6 (Mitogen-Activated Protein Kinase Kinase 6):

MAP2K7 (Mitogen-Activated Protein Kinase Kinase 7):

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... More...

MAP3K11 (Mitogen-Activated Protein Kinase Kinase Kinase 11):

Immunohistochemistry of Human liver cancer using MAP3K11 Polyclonal Antibody at dilution of 1:40

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... More...

MAP3K12 (Mitogen-Activated Protein Kinase Kinase Kinase 12):

MAP3K2 (Mitogen-Activated Protein Kinase Kinase Kinase 2):

MAP3K3 (Mitogen-Activated Protein Kinase Kinase Kinase 3):

MAP3K4 (Mitogen-Activated Protein Kinase Kinase Kinase 4):

MAP3K5 (Mitogen-Activated Protein Kinase Kinase Kinase 5):

ARAF (V-Raf Murine Sarcoma 3611 Viral Oncogene Homolog):

BRAF (V-Raf Murine Sarcoma Viral Oncogene Homolog B1):

RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1):

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]. More...

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... More...

RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1):

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... More...

HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog):

Western blot analysis of Hela, HepG2 and 231 cell, Mouse kidney tissue, using HRAS Polyclonal Antibody at dilution of 1:200

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... More...

Activators

CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)):

Western blot analysis of CDC42 Antibody (Center) (ABIN390921) in NCI-H460 cell line lysates (35 µg/lane). CDC42 (arrow) was detected using the purified polyclonal antibody.

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... More...

PAK1 (P21-Activated Kinase 1):

Western blot analysis of extracts from 3T3 cells, treated with UV (15mins), using PAK1 (epitope around residue 204) antibody.

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... More...

GCK (Glucokinase (Hexokinase 4)):

NRAS - GTPase NRas:

MAP4K3 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 3):

PAK2 (P21-Activated Kinase 2):

HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog):

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... More...

BCL2 (B-Cell CLL/lymphoma 2):

Immunohistochemical analysis of paraffin-embedded human breast carcinoma tissue using BCL-2 (Ab-70) antibody (E021060).

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... More...

BAD (BCL2-Associated Agonist of Cell Death):

Western blot analysis of extracts from 293 cells using BAD (Ab-155) antibody (E021064).

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,... More...

BTG2 (BTG Family, Member 2):

BTG2 Antibody (N-term) western blot analysis in K562 cell line lysates (35ug/lane).This demonstrates the BTG2 antibody detected the BTG2 protein (arrow).

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]. More...

CANX - Calnexin

Lane 1: MarkerLane 2: Hela cell lysateLane 3: HEK293 cell lysateLane 4: NIH/3T3 cell lysateLane 5: HepG2 cell lysateWestern blot analysis of cell lysates using 1 µg/mL Rabbit Anti-Calnexin Polyclonal Antibody (ABIN398769) The signal was developed with IRDyeTM 800 Conjugated Goat Anti-Rabbit IgG.

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... More...

CASP9 - Caspase 9

Western blot analysis of extracts from 293 and Hela cells using 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... More...

MAPK

MAPK14 (Mitogen-Activated Protein Kinase 14):

MAPK1 - ERK2

MAPK10 (Mitogen-Activated Protein Kinase 10):

MAPK11 (Mitogen-Activated Protein Kinase 11):

MAPK12 (Mitogen-Activated Protein Kinase 12):

MAPK13 (Mitogen-Activated Protein Kinase 13):

MAPK14 (Mitogen-Activated Protein Kinase 14):

MAPK3 (Mitogen-Activated Protein Kinase 3):

MAPK4 (Mitogen-Activated Protein Kinase 4):

MAPK6 (Mitogen-Activated Protein Kinase 6):

MAPK7 (Mitogen-Activated Protein Kinase 7):

MAPK8 - JNK:

MAPK9 (Mitogen-Activated Protein Kinase 9):

MAP2K

MAP2K1 (Mitogen-Activated Protein Kinase Kinase 1):

MAP2K2 (Mitogen-Activated Protein Kinase Kinase 2):

MAP2K3 (Mitogen-Activated Protein Kinase Kinase 3):

MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4):

MAP2K5 (Mitogen-Activated Protein Kinase Kinase 5):

MAP2K6 (Mitogen-Activated Protein Kinase Kinase 6):

MAP2K7 (Mitogen-Activated Protein Kinase Kinase 7):

MAP3K

MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1):

MAP3K11 (Mitogen-Activated Protein Kinase Kinase Kinase 11):

MAP3K12 (Mitogen-Activated Protein Kinase Kinase Kinase 12):

MAP3K2 (Mitogen-Activated Protein Kinase Kinase Kinase 2):

MAP3K3 (Mitogen-Activated Protein Kinase Kinase Kinase 3):

MAP3K4 (Mitogen-Activated Protein Kinase Kinase Kinase 4):

MAP3K5 (Mitogen-Activated Protein Kinase Kinase Kinase 5):

ARAF (V-Raf Murine Sarcoma 3611 Viral Oncogene Homolog):

BRAF (V-Raf Murine Sarcoma Viral Oncogene Homolog B1):

RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1):

RAF

ARAF (V-Raf Murine Sarcoma 3611 Viral Oncogene Homolog):

BRAF (V-Raf Murine Sarcoma Viral Oncogene Homolog B1):

RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1):

RAS

NRAS - GTPase NRas

HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog):

Activators

CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)):

PAK1 (P21-Activated Kinase 1):

GCK (Glucokinase (Hexokinase 4)):

NRAS - GTPase NRas:

MAP4K3 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 3):

PAK2 (P21-Activated Kinase 2):

HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog):

Targets

ATF2 (Activating Transcription Factor 2):

BCL2 (B-Cell CLL/lymphoma 2):

BAD (BCL2-Associated Agonist of Cell Death):

BTG2 (BTG Family, Member 2):

CANX - Calnexin

CASP9 - Caspase 9

CDT1 (Chromatin Licensing and DNA Replication Factor 1):

CTTN - Cortactin:

DAPK1 - DAP Kinase 1:

ELK1 (ELK1, Member of ETS Oncogene Family):

EIF4EBP1 (Eukaryotic Translation Initiation Factor 4E Binding Protein 1):

GJA1 (Gap Junction Protein, alpha 1, 43kDa):

HSPB1 (Heat Shock 27kDa Protein 1):

HSF4 (Heat Shock Transcription Factor 4):

MCL1 - MCL-1:

JUN - C-JUN:

MKNK1 (MAP Kinase Interacting serine/threonine Kinase 1):

MKNK2 (MAP Kinase Interacting serine/threonine Kinase 2):

MAPT (Microtubule-Associated Protein tau):

MAPKAPK2 - MAPKAP Kinase 2:

MAPKAPK3 - MAPKAP Kinase 3:

MAPKAPK5 - MAPKAP Kinase 5:

PXN - Paxillin:

PPARG (Peroxisome Proliferator-Activated Receptor gamma):

RGS1 (Regulator of G-Protein Signaling 1):

RPS6KA1 (Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 1):

RPS6KA2 (Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 2):

RPS6KA3 (Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 3):

RPS6KA5 (Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 5):

RPS6KA6 (Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 6):

SGK1 (serum/glucocorticoid Regulated Kinase 1):