4 replies to this topic

[gyma]

Hi everyone. I am now working on a cancer-related gene, or a ligand more accurately. I found this gene is overexpressed in cancer patients but I am not clear about the downstream of this gene. For example, there is a receptor family including more than 10 members which are all possible receptors to this ligand. There are some papers about its receptor but it looks like the receptor varies in different cell/tissue types. So I have to find out its receptor in my research.
I have tested the expression of several candidate receptors when this ligand is knocked down. Some are downregulated but some remain unaffected. I am now a little confused looking at this result. I thought if this ligand-induced signal is critical, when it is knocked down, expression of its receptor should be upregulated, as a signal requesting more ligands. I dont know whether my thought is ture. Is there a feedback, what is it?
How could I find out the receptor? any methodological advice? thank you very much.

[EvilTwin]

There are many mechanisms of a cell response to a stimulation and other regulating receptor expression. They don't need to be  intertwined so tightly. As far as I understand you think that a cell "wants" to recieve a signal and if it doesn't, it produces more receptor to increase it's sensitivity.  Even if upregulation of a receptor after eliminating ligand takes place in a few receptor-ligand interactions it doesn't have to be a rule.
If you can somehow inhibit these receptors specifically (or at least divide them into groups that respond to different inhibitors) you may try to asses cell's response to the ligand after inhibiting chosen receptors.

Edited by EvilTwin, 17 April 2012 - 01:46 AM.

[gyma]

EvilTwin, on 17 April 2012 - 01:44 AM, said:

There are many mechanisms of a cell response to a stimulation and other regulating receptor expression. They don't need to be intertwined so tightly. As far as I understand you think that a cell "wants" to recieve a signal and if it doesn't, it produces more receptor to increase it's sensitivity. Even if upregulation of a receptor after eliminating ligand takes place in a few receptor-ligand interactions it doesn't have to be a rule. If you can somehow inhibit these receptors specifically (or at least divide them into groups that respond to different inhibitors) you may try to asses cell's response to the ligand after inhibiting chosen receptors.

Thank you. I have thought of using antibodies to those receptors but it will cost a lot and also those antibodies might not always be able to block the receptors. And also it looks like not very efficient because I have to test them one by one. However, if I am able to find a method to pinpoint several candidates, then the job will become easier. That is why I asked this question. Do you know any other methods?

[EvilTwin]

What kind of receptors are they? Perhaps they have specific chemical inhibitor of the effector domain.

[gyma]

they are receptors for Wnt ligands, such as FZD family, ROR1, ROR2......