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1.Erk signaling overview
The extracellular-signal-regulated kinase (ERK) pathway is one of the major signaling
cassettes of the mitogen activated protein kinase (MAPK ) signaling pathway. The ERK
cascade is activated by a variety of extracellular agents, including growth factors,
hormones and also cellular stresses to induce cellular processes that include mainly
proliferation and differentiation, but under some conditions also stres s response and others.
The main MAPK/ERK kinase kinase (MEKK) components are the Raf family members Raf-1,
A-Raf and B-Raf that phosphorylate two serine residues on the MAPK/ERK kinase (MEK)
components MEK1/2. ERK1/2 are responsible for stimulating the downstream effectors,
many of which are transcription factors. One of the major transcription factors is cyclic AMP
response element-binding protein (CREB).
2.Erk signaling cascade
The activation of the ERK1/2 cascade is mostly initiated at membrane receptors, such as
receptor Tyr kinases (RTKs), G protein–coupled receptors (GPCRs), ion channels, and
others. These receptors transmit the signal by recruiting adaptor proteins (e.g., Grb2) and
exchange factors (e.g., SOS) that, in turn, induce the activation of Ras at the plasma
membranes, or membranes of other organelles. The activated, GTP bound Ras then
transmits the signal by activating the protein kinases Raf-1, B-Raf, and A-Raf (Rafs) within
the MAP3K level of this cascade. This activation occurs by recruiting Rafs to the
membranes, where they are then phosphorylated and activated.