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MAPK Signaling

Written/Edited by Dr. Stefan Pellenz, PhD

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.

References:

Pearson, Robinson, Beers Gibson, Xu, Karandikar, Berman, Cobb: "Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions." in: Endocrine reviews, Vol. 22, Issue 2, pp. 153-83, (2001) (PubMed).

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 - ERK1:

MAPK4 (Mitogen-Activated Protein Kinase 4):

MAPK6 (Mitogen-Activated Protein Kinase 6):

MAPK7 (Mitogen-Activated Protein Kinase 7):

MAPK8 - JNK:

MAPK9 - JNK2:

MAP2K

MAP2K1 - MEK1:

MAP2K2 - MEK2:

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 - ASK1:

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

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

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

RAF

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

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

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

RAS

NRAS - GTPase NRas:

HRAS (HRas proto-oncogene, GTPase):

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 (HRas proto-oncogene, GTPase):

Targets

ATF2 (Activating Transcription Factor 2):

BCL2 - Bcl-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 - eIF4EBP1:

GJA1 - Connexin 43/GJA1:

HSPB1 - HSP27:

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 - MSK1:

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

SGK1 (serum/glucocorticoid Regulated Kinase 1):

SIRT1 (Sirtuin 1):

Sorbs3 - Vinexin:

SPZ1 (Spermatogenic Leucine Zipper 1):

STMN1 - Stathmin 1:

TP53 - p53:

YAP1 (Yes-Associated Protein 1):

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