Page 79 - 85 cell signalling pathways

Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 79

Module 2: Figure reversible and irreversible ROS oxidations

Protein N H
substrate S * Grx and Trx
N systems
SH S 8
H O
2
H O 2 2
1 SH
H O 2
2
N H N H
Sulphenic H O
acid SOH 3 2
S
SH S
H O 2
2
5 GSH 4 N H
H O SSG
2
N H H O
Sulphinic 2
acid SO H SH
2
7
SH
Srx N H O
H O 2 S
2
6 ATP PO 4
H O
2
N H SH
Sulphonic
acid SO H
3
SH
Reactive oxygen species (ROS) messenger action through the reversible oxidation of target proteins.
The target protein (blue) undergoes a variety of oxidative covalent modifications, some of which induce the conformational changes responsible for
mediating a variety of oxidation-sensitive processes. The target proteins that are modified by reactive oxygen species (ROS) have a hyperreactive
cysteine thiolate anion (asterisk) that is highly sensitive to oxidation by H 2 O 2 to initiate a cascade of reactions as described in the text.
Module 2: Figure ROS formation and action
Growth
factors
Cytokines Hormones

NOX/DUOX

Protein PI 3-K PIP PIP PIP 2
kinase 3 3
P
Signalling Signalling
-SH
protein protein H 2 O 2 PTEN -SH S
S SH 1 2 Trx S
Trx PTP
S N H
-SH
S Trx -SH
PTEN
-SH PTP S S
N
Trx -SH
Inactivated PTEN
Inactivated protein
tyrosine phosphatase (PTP)

Formation of H 2 O 2 and its action to regulate phosphotyrosine phosphatase (PTP) and phosphatase and tensin homologue deleted on chromo-
some 10 (PTEN).
The hydrogen peroxide (H 2 O 2 ) formed by the NADPH oxidase (NOX)/DUOX (dual oxidase) complex creates a microdomain in which it can inactivate
enzymes involved in various signalling pathways: 1. The phosphotyrosine phosphatase (PTP) that dephosphorylates various signalling proteins is
inactivated following its oxidation by H 2 O 2 ; 2. The inositol lipid phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which
dephosphorylates the lipid second messenger PtdIns3,4,5P 3 , is inactivated following its oxidation by H 2 O 2 . These two enzymes can be reactivated
following their reduction by the thioredoxin (Trx) system (Module 2: Figure recovery of protein oxidation).

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