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Signalisation MAPK

La phosphorylation est le processus réversible d'addition d'un groupe phosphate à un résidu spécifique d'acide aminé sur une molécule. Sur le plan fonctionnel, la phosphorylation agit comme un simple commutateur moléculaire qui peut activer, désactiver ou moduler la fonction d'une protéine. L'addition et l'enlèvement de groupes phosphates permettent le contrôle spatial et temporel de l'activité de la protéine. La phosphorylation est bien contrôlée par un réseau interdépendant concourant de kinases (addition de groupe phosphate à une protéine substrat) et de phosphorylases (enlèvement de groupe phosphate de ce substrat).

Les protéines kinases activées par des agents mitogènes (MAPKs) sont une famille d'enzymes kinases bien conservées et exprimées ubiquitairement, qui phosphorylent différents substrats cibles. Les MAP-kinases font partie d'une cascade de phosphorylation plus grande à plusieurs niveaux incluant les MAP2Ks et MAP3Ks. Cette organisation à plusieurs niveaux offre une plus grande flexibilité, permettant à une large gamme de kinases d'ordre supérieur de répondre aux stimuli et de contrôler la fonction cellulaire par l'activation d'un sous-ensemble plus petit de MAP-kinases qui interagissent directement avec d'autres protéines fonctionnelles.

Les MAP-kinases jouent un rôle important dans pratiquement tous les processus cellulaires. La phosphorylation dépendant de la MAPK est impliquée dans les cascades de signalisation qui régulent la progression, la différentiation, le développement et l'apoptose du cycle cellulaire.

Lectures supplémentaires : Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH (Avril 2001). "Voies de protéines kinases activées par des agents mitogènes (MAP) : régulation et fonctions physiologiques". Endocr. Rev. 22 (2): 153–83. doi:10.1210/er.22.2.153. PMID 11294822.

MAPK

MAPK14 (Mitogen-Activated Protein Kinase 14):

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):

MAPK4 (Mitogen-Activated Protein Kinase 4):

MAPK7 (Mitogen-Activated Protein Kinase 7):

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...   More...

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...   More...

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):

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):

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 (B-Raf proto-oncogene, serine/threonine kinase):

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...

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 (HRas proto-oncogene, GTPase):

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)):

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):

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...

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

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):

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):

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):

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

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

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...

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

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

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

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

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