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GTP-binding proteins and protein phosphorylation

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).

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GTP-binding proteins and protein phosphorylation

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  1. GTP-binding proteins and protein phosphorylation

  2. I

  3. Signal transduction, from a first messenger binding to its receptor, to an immediate response, followed by a change in gene expression (cellular plasticity)

  4. GTP-binding proteins or GTPases: transient modification through the replacement of GDP by GTP

  5. The generic GTPase cycle (acting as a metastable switch)

  6. GTP / GDP exchange as a means to alter protein configuration and activity Ras GDP Ras GTP

  7. Ras domains Protein domains of Ras and conservation of the GTP binding site P-loop

  8. Ras regulators Regulators and effectors of Ras

  9. Monomeric GTPases are involved in: -Vesicle formation -Vesicle targeting and fusion -Nuclear transport -Regulation of actin cytoskeleton -Protein synthesis -Signaling from growth factor receptors

  10. GTP / GDP exchange as a means to alter protein configuration and activity !

  11. Heterotrimeric GTPases are involved in signaling of: -Adrenergic amines -Acetylcholine (musc) -Chemokines -Neurotransmitters -Glucagon -Thyrotropin -Tastants -Light (rhodopsin) -Thrombine -Odarants

  12. 2) Protein phosphorylation: transient modification through covalent binding of Pi

  13. Glycogen phosphorylase; first discovery of protein phosphorylation and its effect on enzyme activity (Krebs and Fisher, 1956) Image: D.Goodsell

  14. Image G. Johnson

  15. Image: D. Goodsell

  16. 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

  17. 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 »

  18. 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 2 3 1 4 6 5

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