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Re: question » Elizabeth

Posted by Cam W. on September 18, 2001, at 8:45:24

In reply to question » Cam W., posted by Elizabeth on September 17, 2001, at 10:07:20

Elizabeth - Simply stated, second messengers initiate the cascade of chemical reactions on the interior of a cell caused by a signal (produced by the binding of a molecule to a receptor on the exterior cell surface). This cascade of chemical reactions ultimately results in the transcription of genes, that will become enzymes and proteins.

The enzymes or proteins that are produced depends upon what exterior receptor is stimulated and by what molecule stimulates (or blocks) said receptor Different conformational changes in the receptor may be produced by the binding of slightly different molecules to that receptor, hence different shapes will occur on the other end of the protein (inside the cell).

Second messengers can take many forms and (I think) are driven by ATP or GTP being converted to AMP or GMP, respectively. The main second messenger is usually a G-protein. A G-protein binds to the transmembrane protein and causes a cascade of other molecules to bind to it in a very specific way (I think that the conformation of the piece of transmembrane protein sticking through to the interior of the cell dictates the type of G-protein it attracts, as well as the complement of associated molecules - I am not sure on this point, nor am I sure if the associated molecules are also referred to as secondary messengers, even though they are an integral part of the second messenger process).

An example of G-protein (second messenger) mediated intracellular reaction is the phosphoinositol pathway. Calcium ions are released from the endoplasmic reticulum, thus affecting a neuron's electrical gradient without much interference from ion channels. The exterior cellular surface receptor (protein) still spans the cell wall, but does not open into an ion channel. The conformational change of the interior portion of the protein attracts the G-protein, setting up the cascade and causing the release of calcium ions and these calcium ions further cause the release of gene products (enzymes &/or proteins). Also DAG (diacylglycerol) is released which signals PKC (protein kinase-C) which signals other G-proteins by crosstalking with other cells (PKC) is able to leave the cell and inform surrounding cells of the state of regional homoeostasis. PKC also signals the nucleus to get ready to respond with gene products.

I guess the G-protein is the quarterback of second messengers and it's complement of other molecules are the rest of the team.

Again, basically second messengers carry a signal from a receptor to the nucleus and RNA. As can be seen above (and this is only one, albeit sketchy, example of a second messenger system). There are many other second messenger systems. Since they are so specific, one could wonder about making "magic bullet" drugs to affect specific targets to" shut down" or to "fix" the signal between receptor and the transcription of gene products.

Sorry Elizabeth, this is all I can remember, without digging out my journal articles (they are still packed away in boxes, in the garage).

Take care, and I hope that this makes some sense. - Cam


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