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Q: signaling cascade (molecular biology) ( Answered,   1 Comment )
Subject: signaling cascade (molecular biology)
Category: Science > Biology
Asked by: kelly4help-ga
List Price: $10.00
Posted: 08 May 2005 18:15 PDT
Expires: 07 Jun 2005 18:15 PDT
Question ID: 519330
Hey everyone, I was doing some work for biology and I got stuck on
this problem. Can anyone figure it out and explain it please? Thanks
in advance!

In muscle cells, epinephrine binds to the Beta-adrenergic receptor to
initiate a signaling cascade that leads to the breakdown of glycogen.
At which points in this pathway is the signal amplified?

A critical feature of all signaling cascades is that they must be
turned off rapidly when the extracellular signal is removed. Examine
the signaling cascade in the chart (the link) and describe how each
component of the pathway is returned to its inactive state when
epinephrine is removed
Subject: Re: signaling cascade (molecular biology)
Answered By: andrewxmp-ga on 09 May 2005 21:18 PDT
Hi kelly, 

There are three ways that this signaling cascade is deactivated. 
First and foremost, the ligand itself (adrenaline) has a particular
binding affinity to the extracellular domain of the receptor and will
disassociate in some time depending on that affinity.  This could be
considered passive deactivation because nothing is done to reverse the
physical changes that occured at activation, but the activation has
been stopped.

Second, as mentioned in the comment, the alpha subunit of the mobile
G-protein has an intrinsic GTPase activity, and will cleave GTP into
GDP and Pi after some intrinsic period of time that is not too
important for this question.  This again could be considered passive
deactivation, because the end-result physical changes of the pathway
have not been reversed, however the activation has been stopped.

Third, there are a series of phosphatase enzymes tha serve the purpose
of removing phosphates from particular molecules, and each is quite
specific.  There are phosphatases for each of the molecules that get
phosphorylated in this diagram: phosphorylase kinase, glycogen
phosphorylase, and glycogen.

What we are really concerned with in this pathway is the end product:
the phosphorylation of glycogen, because this is the first step in the
sequence necessary to metabolize it.  So, although it is mostly
triggered by altogether seperate signaling sequences, the
dephosphorylation of glycogen is the most obvious reversal of this
pathway, and it occurs via a specific phosphatase for G1P, as do
glycogen phosphorylase and phosphorylase kinase.

I'll also aswer the question of, "at which point is the signal
amplified."  Generally, signal amplification occurs at the point of
the second messengers, of which cAMPis a very common one.  the
g-protein is not an amplification because there is a 1-to-1 number of
them compared to ligand-bound receptors.  The phosphorylation of
phosphorylase kinase as well as glycogen phosphorylase can be
considered amplification steps as well because the activated PKA,
phosphorylase kinase, or glyogen phosphorylase molecules can each
further phosphorylate MANY of their target molecules.

I hope this has been helpful.  Please feel free to request further
clarification, especially before rating this answer.  Thank you for
using Google Answers!


Request for Answer Clarification by kelly4help-ga on 10 May 2005 04:51 PDT
Dear andrew,

    Thank you sooooo much for the help. However, i still need some
clarifications. This question is related to the diagram. The questions
asks how each componenet of the pathway is returned ot its inactive
state WHEN EPINEPHRINE IS REMOVED. There appears to be four components
of this diagram and i need to know how each of those are returned to
its inactive state when epinephrine is removed. It's a fairly specific
question, so could you provide some further clarifications in terms of
each component of the pathway and provide details as to why it
happens. In addition, the questions stating: at which
points..."..seems to state that there are more than one point where
this pathway has signal that's amplified whereas you've stated only 2
but provided only brief explanations for them. Could you, once again,
provide some further details and clarifications. The information you
have porvided has beeen soo much helpful but i really feel that with
more clarifications, i will fully be able to comprehend this question.
Thank you soo much andrew as you have been extremely nice in helping
me out. I highly appreciate it.



Clarification of Answer by andrewxmp-ga on 12 May 2005 09:57 PDT
Well there are certain activities that go on that serve to reverse
thiw process, but the removal of adrenaline does not really trigger
them.  The removal of adrenaline really just stops the signaling
cascade from moving forward in it's usual fashion, brecause there is
no longer any positive stimulus.  There are however some other
mechanisms in play that serve to reverse this pathway, however they
are not in any way activated by the removal of adrenaline.
First, adenylyl cyclase does not have a particular enzyme that will
"shut it off" per se, it is simply no longer activated when the
g-alpha subunit stops circulating.  This occurs natuarally after a set
period of time after which it catalyzes GTP into GDP, thereby causing
it to reform with the beta and gamma subunits on the membrane protein.
 Second, the enzyme phosphodiesterase (PDE) is upregulated by the
increased levels of cAMP, and it's job is to degrade cAMP so it is no
longer activating PKA and the rest of the pathway downstream.  The
other signaling molecules have their own enzymes that reverse their
activity: glycogen phosphorylase is deactivated by glycogen
phosphorylase phosphatase and phosphorylase kinase is deactivated by
phosphorylase kinase phophatase.  Clearly the names are confusing and
redundant, but they make some sense: phosphorylated molecules are
generaly on or active, and therefore phosphatase enzymes that remove
those phosphates will deactivate them.

I'm not sure exactly what else you're trying to figure out here. 
There are ALWAYS more details to be discussed in complicated pathways
such as this, but I think this covers the basic enzymes and their
regulatory molecules?
Subject: Re: signaling cascade (molecular biology)
From: xarqi-ga on 08 May 2005 19:32 PDT
Here's a start:
Amplification occurs with the continuing creation of cAMP from ATP
while adenylyl cyclase is active.

Deactivation occurs by the inherent GTPase activity of the G-protein
receptor which spontaneously returns it to its inactive form in the
absence of stimulation.

(I think)

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