[ Follow Ups ]
Posted by Sergei on May 10, 1999 at 10:06:36:
In Reply to: Interesting paper (about an insulin mimetic) posted by Jim Till on May 09, 1999 at 10:30:39:
This discovery is fascinating in many aspects.
First, this is a vivid example of how relative non-specificity of a receptor
can be beneficial, particularly in medicine, where any kind of sloppiness is a
potential disaster. Here, receptor sloppiness is used as a success. In a sense,
this is an example of artificial "micro-evolution", because we have
been able to select artificially from a huge repertoire of all possible
"non-intented" ligands.
Second, an example of natural selection around the insulin receptor already
took place. In particular, insulin receptor system and IL-4 receptor system
share a lot of similarity. For example, IL-4 receptor signaling can go through
the Insulin Receptor Substrate (IRS) phosphorylation (see, for example, White
MF. The IRS-1 signaling system. Curr Opin Genet Dev 4(1):47-54,1994). Moreover,
IL-4 receptor system and IL-13 receptor system overlap significantly, and even
involve similar receptor chains, so that most frequently the term
"IL-4/IL-13 receptor" is used now days.
This observation leads to my third point, namely a tremendous non-specificity
of signal transduction pathways. An interesting question is how do different
cytokine manage to exert more a less specific action on cells, whereas their
signaling pathways overlap so much. We already had a brief discussion on this
subject (I will try to find it and will post below as followups to this
message).
Finally, this finding does not surprise me at all. I am actually amazed that we
do not have much more of this kind. It also proves that the HBG vision of
biology is correct, which is satisfying.