By Novartis Foundation, Johannes D. Veldhuis
This fascinating publication brings jointly a world and interdisciplinary team of specialists to debate the significance of pulsatile signalling within the induction of organic responses. assurance contains the fundamental mechanisms curious about hormone pulsatility, the importance of pulsatility in common and affliction stipulations, the relevance of circadian rhythms, alterations with growing old, and unique attention of particular peptide hormone platforms. This publication contains contributions from pros operating in either easy and scientific learn and divulges a lot new and interesting paintings during this sector and gives you new study instructions.
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Additional info for Mechanisms and Biological Significance of Pulsatile Hormone Secretion (Novartis Foundation Symposia)
24 GOLDBETER ET AL The above results on oscillations and frequency encoding have been obtained in a model based on receptor desensitization. Recent observations suggest that intracellular regulatory processes also play a role in controlling the response of the cells to cAMP signals (S˛derbom & Loomis 1998). We are currently extending the model for cAMP signalling to incorporate the control of adenylate cyclase by a cascade of phosphorylations triggered by the binding of extracellular cAMP to its receptor.
If the kinase is activated by Ca2+, oscillations in cytosolic Ca2+ will be accompanied by a periodic increase in the level of phosphorylated substrate, which could mediate the cellular response to stimulation. 30 GOLDBETER ET AL FIG. 7. Phosphorylation curves of three substrates phosphorylated by the same kinase but dephosphorylated by distinct phosphatases, during the course of Ca2+ oscillations. If the phosphatase is less active (a), the level of phosphorylated target protein will be larger. The same frequency of Ca2+ oscillations can thus be transduced into di¡erent levels of phosphorylated proteins.
The encoding of Ca2+ oscillations then occurs in terms of the mean level of a phosphorylated target protein (Goldbeter et al 1990, Dupont & Goldbeter 1992). Given the same Ca2+activated kinase, the mean level of phosphorylated target protein will be governed by the rate of dephosphorylation by the phosphatase. Shown in Fig. 7 are three phosphorylation curves corresponding to the same kinase coupled to three di¡erent phosphatases characterized by di¡erent maximum rates. The results indicate that in such conditions the same frequency of Ca2+ oscillations can be transduced into three di¡erent levels of phosphorylated target proteins, which in turn induce various levels of activation of Ca2+-mediated responses involving the same kinases.