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

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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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