First messenger signals

We have seen that a series of first messenger signaling molecules produce arachidonate mobilization by activating membrane receptors. Too many such effects have been described over the past 20 years to allow me to compile a review of this subject area that is both exhaustive and useful. I will rather illustrate with some examples what I consider to be the three major modalities of receptor-mediated control of arachidonate mobilization stimulation, inhibition and facilitation. Where possible, I will also indicate the specific transmembrane signaling pathway and enzyme route affected. 

Stimulation of a cell by first messengers that increase cellular Ca2+ concentrations similarly activates CREB (Fig. 23-9). This appears to occur via the phosphorylation of CREB on serine 133 by a CaMK, probably CaMKIV as well as, possibly, CaMKI. It remains to be established whether the activated kinase translocates to the nucleus, by analogy with the catalytic subunit of the cAMP kinase, or whether elevated Ca2+ signals enter the nucleus and activate the kinase already there. Interestingly, phosphorylation of CREB on a distinct serine residue, serine 142, by CaMKII appears to inhibit the transcriptional activity of CREB in vitro, although whether this inhibitory effect occurs in vivo is unknown. 

Cells respond to their environment by taking cues from hormones or other external chemical signals. The interaction of these extracellular chemical signals ( first messengers ) with receptors on the cell surface often leads to the production of second messengers inside the cell, which in turn leads to adaptive changes in the cell interior (Chapter 12). Often, the second messenger is a nucleotide (Fig. 8-42). One of the most common is adenosine 3, 5 -cyclic monophosphate... 

Figure 4.9 The first messengers of cell signalling are qualitatively and quantitatively different from the second messengers, and the latter consist of only four basic types of molecular cascades.

It would be possible to manage without codes, for example, if every first messenger could set in motion a unique set of second messengers - as illustrated in Figure 4.10A - because in this case the signals would still be able to instruct the genes even without reaching... 

Figure 4.10 The first messengers of cell signalling can be processed in a variety of ways. Different signals can have the same effect and equal signals can lead to different results, thus showing that signal transduction is based on organic codes.

Plasma membrane receptors are critical to the process of transmitting the information carried by the ligand or first messenger (neurotransmitter, hormone, etc.) from the extracellular space to the cell interior. However, cell signaling requires information flow inside the cell too. The molecules that carry this information to modulate the activity of ion channels, enzymes or receptors are sometimes referred to as second messengers. However, due to the complexity of signal transduction... 

FIGURE 20.2 The different processes within pharmacodynamics. The biophase kinetics account for distributional kinetics between the plasma and effect site. The biosensor kinetics describe the dynamic behavior between drug and biosensing machinery. The biosignal is the first messenger in the transduction process that converts the signal to secondary messengers or the observed response. (Adapted from Ref. 19.)... 

The second messenger is an effector molecule synthesized when a hormone (the first messenger) binds. It stimulates the cell to respond to the original signal. Second messengers also 17.3 allow the signal to be amplified. 

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