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Structure-function of cellular mediators (and receptors)

Jean-Philippe GERARD j-p.g at wanadoo.fr
Sun Feb 28 19:47:56 EST 1999


I ask myself some peculiar questions about intercellular 
messengers, and could not find clear answers up to now.


I wonder if the mediators of whatever activity
   (neurologic, endocrine, immunologic, etc.) 
which are known to work through 
their interactions with a specific receptor 
triggering a cascade of intra-cellular events
   (eventually through secondary messengers or ions
    cAMP, G-proteins, P-inositides, Ca++, etc.)
could not act by other means.

For exemple :
gamma-Interferon has two types of biologic activity : 
antiviral and immunologic
              (expression of MHC II°°°),
Gamma-IFN is also species-restricted :
mouse-gIFN doesn't work on human-gIFN (and reciprocally) :
no binding on the membrane receptor even if 
there is a quite close sequence relationship.

   °°° MHC II : Major Histocompatibility Complex type II


But, if you microinject h-gIFN in mouse cells
these cells do express MHC II antigens.
   (same thing transfecting mouse cells w/ human-gIFN gene)
but you don't protect them against viral infection.

Strange enough.

It looks like that there is some kind of
intra-cellular receptor which could recognize a part
of the polypeptide chain of gIFN or one of its fragment,
and one of the function of the cellular receptor 
would be to permit internalization of the messenger.

This could be generalized :
peptidic or proteinic cytokines acts also
through multiple intra-cellular cascade triggered 
by the internalized and digested peptides.
It could also explain the partial community od 
biological activity of similar cytokines
which do not bind the same receptor.
and it address in a much better way the response specificity
than second messanger cascades (but G-proteins) :
cAMP, cGMP, Ca++, inositides, etc.

------------------

Interferon like many cytokines is a homomultimer.
(usually di- or trimer).

Is it possible to imagine, that in these tight little boxes
(or "shields") there is a metal (Cu, Fe, Co, Zn, etc.), 
or a non-metallic element (B, Si, Se, etc.) 
eventually stabilized in a particular (hyper)valent state
(which would be unstable otherwise) ?

Cytokines as shuttles ?
   (eventually to evacuate these elements from the cell :
    kind of detoxification or to permit cellular progression 
    in mitosis, etc.)

This question could also be asked for non-peptidic
messengers : could they also act through the transport 
of (more or less) specifically associated (chelated) ions ?
I think particularly about trace elements.


Thank's in advance for any reflexion
or any bibliographic reference 
addressing these questions.


Jean-Philippe GERARD   
(in FRANCE)



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              j-p.g at wanadoo.fr          _____  __o            --  <^_
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The goal of life is to die young as late as possible. - Ashley MONTAGU -



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