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transduc.on 3
cAMP
cGMP
IP3
DAG
Ca2+
Second messengers
Ca 2+
Reception
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Inactive G protein
Active G protein (102 molecules)
ATP
Cyclic AMP (104)
Protein Kinase
OH + ATP
Protein
Protein
+ ADP
O
Pi
H2O
Protein Phosphatase
w A protein kinase transfers the phosphate group of a donor molecule (such
as ATP) to a hydroxyl group on a protein.
w A protein phosphatase catalyzes removal of the Pi by hydrolysis.
10
11
factor (PDGF)
13
14
Phosphorylation may directly alter with a switch mechanism the biological activity
or subcellular localization of a protein or enzyme, e.g.
by promoting reversible changes in the affinity for
specific molecules, due to
inter-molecular repulsion/attraction events
isocitrate dehydrogenase
by promoting reversible conformational changes
that modulate the enzymatic activity, due to the
formation of novel hydrogen bonds or
repulsion/attraction of intra-molecular charged
regions
glycogen phosphorylase
MAPKs and RTKs
Src
Cdks
by promoting reversible formation of consensus
sites for binding of proteins that specifically
recognize phosphorylated domains. This
mechanism involves changes in subcellular
localization
PhosphoTyr / protein containing PTB/SH2 domains
PhosphoSer or PhosphoThr / 14-3-3 protein
15
Example of cooperative
phosphorylation
19
Boggon and Eck Structure and regulation of Src family kinases Oncogene (2004) 23, 79187927
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
Pi
ADP
Active
protein
kinase
2
PP
Inactive
protein kinase
3
ATP
Pi
ADP
Active
protein
kinase
3
PP
Inactive
protein
ATP
Pi
PP
ADP
Active
protein
Cellular
response
22
FEBS Journal
Volume 276, Issue 12, pages 3177-3198, 29 APR 2009 DOI: 10.1111/j.1742-4658.2009.07027.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2009.07027.x/full#f8
FEBS Journal
Volume 276, Issue 12, pages 3177-3198, 29 APR 2009 DOI: 10.1111/j.1742-4658.2009.07027.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2009.07027.x/full#f7
FEBS Journal
Volume 276, Issue 12, pages 3177-3198, 29 APR 2009 DOI: 10.1111/j.1742-4658.2009.07027.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2009.07027.x/full#f7
FEBS Journal
Volume 276, Issue 12, pages 3177-3198, 29 APR 2009 DOI: 10.1111/j.1742-4658.2009.07027.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2009.07027.x/full#f7