EGF receptor

Donald Johnston DJ.50 at worldnet.att.net
Wed Mar 19 18:46:57 EST 1997



> To my knowledge no one has ever adequately answered this question.  One
> view is that the "high affinity" receptor population is already
> dimerized, but somehow it is incapable of signal transduction even
> though it is already dimerized.

My reading of EGF-R scatchard analysis vis a vis mutant receptors is that
dimerization is not a factor in defining high and low affinity binding
sites.  On one level it would seem to be simple allostery - binding of one
egf would alter the conformation of the second receptor in the dimer, 
increasing the affinity of the second for egf binding.   

> In my view, you are asking the wrong question.  The real question is:
> "Is the evidence that there are two populations with different
> affinities correct?"  The evidence is that when people study EGF binding
> by Scatchard analysis they get a concave upward Scatchard plot, which
> they then interpret as indicating the presence of two populations. 

> However, this interpretation ignores the question of whether a Scatchard
> analysis makes any sense for this system.  What is almost universally
> ignored is the true stoichiometry of the interaction.  Scatchard
> analysis is fine (tho' certainly not optimal by today's standards for
> non-linear analysis) for a simple 1:1 binding interaction.  However, for
> ANY system where you believe ligand binding leads to receptor
> dimerization a Scatchard analysis is fundamentally, thermodynamically
> just plain WRONG, and what one measures are apparent AVIDITIES, not
> thermodynamic binding affinities.

So, does receptor dimerization occur under the conditions of Scatchard
analysis?

> Furthermore, when the receptor is being dimerized a correct
> thermodynamic analysis predicts that a Scatchard curve MUST be
> non-linear even when all receptors are behaving identically.  This is
> easiest to see if we think in terms of binding energy: if the receptor
> is being dimerized then the APPARENT binding energy of ligand to
> receptor will be the energy of the simple initial 1:1 binding event plus
> some portion of the binding energy responsible for receptor
> dimerization.  

 As I read your interpretation,  a one to one correspondance would be
expected if the receptors did not dimerize. Is this correct?




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