Page 86 - 85 cell signalling pathways

Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 86

Module 2: Table MAPK signalling toolkit Module 2 Table continued
Mitogen-activated protein kinase (MAPK) signalling toolkit Component Comment
Component Comment MAPK phosphatases
Transducers MKP-1 MAPK phosphatase-1 (Module 2:
GCK Germinal centre kinase Figure ERK signalling)
GLK GCK-like kinase MKP-2 MAPK phosphatase-2
HPK1 Haematopoietic progenitor kinase 1 MKP-3 MAPK phosphatase-3, acts
MST1 Mammalian Ste20-like protein kinase specifically to dephosphorylate
ERK2
MAPKKKs MKP-4 MAPK phosphatase-4
ASK1 Apoptosis signal-regulating kinase 1 MKP-5 MAPK phosphatase-5
ASK2 Apoptosis signal-regulating kinase 2 VHR VH1-related
DLK Dual leucine-zipper-bearing kinase
hVH3/B23
MEKK1 MAPK/ERK kinase kinase 1
hVH5/M3/6
MEKK2 MAPK/ERK kinase kinase 2
PAC1
MEKK3 MAPK/ERK kinase kinase 3
Pyst2
MEKK4 MAPK/ERK kinase kinase 4
STEP Striatal-enriched protein tyrosine
MLK1 Mixed lineage kinase 1
phosphatase; dephosphorylates
MLK2 Mixed lineage kinase 2
ERK in neurons (Module 10:
MLK3 Mixed lineage kinase 3
Figure medium spiny neuron
Mos
signalling).
Raf-1
B-Raf
PAK p21-activated kinase
TAK1 TGFβ-activated protein kinase 1
Tpl2 Tumour progression locus 2
Apoptosis signal-regulating kinase 1 (ASK1)
MAPKKs
MEK1 MAPK/ERK kinase 1 Apoptosis signal-regulating kinase 1 (ASK1) is part of
MEK2 MAPK/ERK kinase 2 the mitogen-activated protein kinase (MAPK) signalling
MKK3 MAPK kinase 3 toolkit (Module 2: Table MAPK signalling toolkit)where
MKK4 MAPK kinase 4
MEK5 MAPK/ERK kinase 5 it functions as one of the MAPK kinase kinases (MAP-
MKK6 MAPK kinase 6 KKKs) that operates within the c-Jun N-terminal kinase
MKK7 MAPK kinase 7 (JNK) pathway (Module 2: Figure MAPK signalling). One
MAPKs of the stimuli capable of activating ASK1 is tumour nec-
ERK1 Extracellular-signal-regulated kinase 1 rosis factor α (TNFα) (see step 2 in Module 2: Figure
ERK2 Extracellular-signal-regulated kinase 2
ERK3-related NF-κB activation).
ERK3 Extracellular-signal-regulated kinase 3 The activity of ASK1 can also be modulated by at least
ERK5 Extracellular-signal-regulated kinase 5 two other signalling mechanisms. First, the reduced form
ERK7 Extracellular-signal-regulated kinase 7
ERK8 Extracellular-signal-regulated kinase 8 of the redox buffer thioredoxin (Trx) binds to ASK1 and
JNK1 c-Jun N-terminal kinase 1 inhibits its activity. Following ROS formation, the Trx is
JNK2 c-Jun N-terminal kinase 2 oxidized and dissociates thus removing its inhibitory ef-
JNK3 c-Jun N-terminal kinase 3
p38α fect and allowing ADK1 to stimulate apoptosis. Secondly,
p38β ASK1 activity is inhibited by binding to calcium and in-
p38γ tegrin-binding protein 1 (CIB1).Anincreaseinthe level
p38δ
of Ca 2 + removes this inhibition thus allowing ASK1 to
MAPK scaffolding proteins
β-Arrestin-2 induce apoptosis.
JIP1 JNK-interacting protein 1
JIP2 JNK-interacting protein 2
JIP3 JNK-interacting protein 3 Sprouty (SPRY)
KSR1 Kinase suppressor of Ras 1 There are two families of sprouty proteins that function
KSR2 Kinase suppressor of Ras 2
MP1 MEK partner 1 as inhibitors of the MAP kinase signalling pathway. The
MKPX Phosphatase that may also function as founding sprouty family has four members (SPRY1--4)
a scaffold while the sprouty-related, EVH1 domain-containing pro-
SKRP1 Stress-activated protein kinase (SAPK)
pathway-regulating phosphatase 1 tein (SPRED) family contains three members (SPRED1--
3) together with EVE-3, which is a splice variant of
MAPK target proteins
ATF2 Activating transcription factor 2 SPRED3. Members of this family have a cysteine-rich do-
Cytoplasmic PLA 2 Cytoplasmic phospholipase A 2 main (CRD).
ETS
Elk-1 The SPRY proteins seem to function during develop-
c-Jun ment to control the formation of a number of tissues and
Jun-B organs. The level of SPRY1 is regulated by miR-21 to in-
Jun-D
MAPKAP-kinase MAPK-activated protein kinase crease MAP kinase signalling during cardiac development.
MEF2 Myocyte enhancer factor 2 Like the SPRY family, the SPREDs act by binding to
MSK1 Mitogen- and stress-activated protein either Ras or Raf1 to inhibit the MAP kinase signalling
kinase 1
MSK2 Mitogen- and stress-activated protein pathway. SPRED1 can act either as a homodimer or as a
kinase 2 heterodimer with SPRED2.
SAP-1 Stomach cancer-associated protein Mutations in the gene that encodes SPRED1, which will
tyrosine phosphatase-1
result in hyperactivation of the Ras/MAP kinase signalling

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