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Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 87

Module 2: Figure MAPK signalling

ERK pathway JNK pathway p38 pathway
Growth factors Osmotic stress FasL, Osmotic stress,
Stimulus redox stress, cytokines radiation
radiation
Transducers
Grb2 SOS Rac Cdc42 Rac Cdc42
Ras Rho

MAPKKK Raf-1, A-Raf, B-Raf MEKK1-4, MLK1-3, TAK1, TAK1
ASK1/3, TPL-2

MAPKK MEK1/2 MEK4/7 MEK3

MAPK ERK1/2 JNK1-3 p38

Effectors Ets, Elk1, SAP1 c-Jun, Jun-B, Jun-D, ATF2, Ets, MEF2,
cPLA2 ATF2, Elk1 SAP1, MAPKAP2

Cellular Proliferation Proliferation, apoptosis, Apoptosis, cytokine
responses embryonic development release, cell cycle arrest

Organization of the main mitogen-activated protein kinase (MAPK) signalling pathways.
The generic pathway on the left summarizes the sequential organization of the mitogen-activated protein kinase (MAPK) signalling system. External
stimuli act through a variety of transducers to stimulate the first element of the signalling pathway, which is one of the 14 different MAPK kinase
kinases (MAPKKKs). These MAPKKKs then phosphorylate the next element, which is one of the seven MAPK kinases (MAPKKs). This MAPKK then
phosphorylates one of the 12 MAPKs, the names of which define the different signalling pathways. The three main pathways are the ERK pathway
(Module 2: Figure ERK signalling), the JNK pathway (Module 2: Figure JNK signalling) and the p38 pathway. The components that make up these
different signalling pathways are summarized in the MAPK signalling toolkit (Module 2: Table MAPK signalling toolkit).

Module 2: Figure ERK signalling

Growth factors

GPCR PTKR
Grb2 SOS Ras
PLC Gq P
SHC
Src P Raf-1
2+ P KSR1
Ca
Pyk2 P MEK1/2
+
+
cPLA 2 + PKC P ERK1/2
DAG P
P
+
cPLA 2
ERK1/2
PL
Arachidonic
acid P ERK1/2
P MKP-1
Negative
ETS SAP1 ELK1 feedback
MKP1 loop
Proliferation

The organization and topology of the extracellular-signal-regulated kinase (ERK) pathway.
The extracellular-signal-regulated kinase (ERK) pathway, which can be made up from different components (Module 2: Figure MAPK signalling), is
represented here by Raf-1, mitogen-activated protein kinase (MAPK)/ERK kinase 1/2 (MEK1/2) and ERK1/2, which can be activated by either protein
tyrosine kinase-linked receptors (PTKRs) or by G protein-coupled receptors (GPCRs). (See the text for further details.)

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