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GTP-binding proteins and protein phosphorylation. I. Signal transduction, from a first messenger binding to its receptor, to an immediate response, followed by a change in gene expression (cellular plasticity). - PowerPoint PPT Presentation
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GTP-binding proteins and protein phosphorylation
I
Signal transduction, from a first messenger binding to its receptor, to an immediate response, followed by a change in gene expression (cellular
plasticity)
1) GTP-binding proteins or GTPases: transient modification through the replacement of GDP by GTP
The generic GTPase cycle(acting as a metastable switch)
GTP / GDP exchange as a means to alter protein configuration and activity
Ras GDP Ras GTP
Ras domains
Protein domains of Ras and conservation of the GTP binding site
P-loop
Ras regulators
Regulators and effectors of Ras
Monomeric GTPases are involved in:
-Vesicle formation-Vesicle targeting and fusion-Nuclear transport-Regulation of actincytoskeleton-Protein synthesis-Signaling from growthfactor receptors
GTP / GDP exchange as a means to alter protein configuration and activity
!
Heterotrimeric GTPases areinvolved insignaling of:
-Adrenergic amines-Acetylcholine (musc)-Chemokines-Neurotransmitters-Glucagon-Thyrotropin-Tastants-Light (rhodopsin)-Thrombine-Odarants
2) Protein phosphorylation: transient modification through covalent binding of Pi
Glycogen phosphorylase; first discovery of protein phosphorylation and its effect on enzyme activity (Krebs and
Fisher, 1956)
Image:D.Goodsell
Image
G. Johnson
Image:D. Goodsell
Transient phosphorylation requires the action of both protein kinases, those that add the phosphate(s) and that of protein phosphatases, those that remove the phosphate(s)
Here is an example of a phosphatase being a true « reset button »
Image:D. Goodsell
Transient phosphorylation requires the action of both protein kinases, those that add the phosphoryle group (phosphate), and that of protein phosphatases, those that remove the phosphate.
Here is an example where the phosphatase acts as a « switch-on button »
Signal transduction
cascade:
switching from 1) tyrosine kinase to
2) GTPase,
from 3)serine kinase
to 4) dual specificity
kinase, to
5) serine kinase
and finally to
6) phosphorylation of transcription factors
1
2 3
4
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