ravena at CCO.CALTECH.EDU (Karen Lona Allendoerfer) wrote:
> This newsgroup has just arrived at Caltech, but I haven't been able
>to read any messages posted to it yet.
Welcome to the group. It's only just started!
> What I am puzzled about is what role people think that
>carbohydrates might be playing in proliferation. Are the carbohydrate
>modifications "cause" or "effect," i.e. are they upstream or downstream to
>oncogenic transformation? Are they modifications of protein or lipid
>ligands that enable the ligands to bind better to some putative receptor?
>Are there any candidates for such receptors? There is data showing that
>the selectin family binds to Si-LeX, but are selectins also associated with
>or re-expressed during normal or abnormal proliferation? What about signal
>transduction events associated with carbohydrate binding?
I'm only one of the discussion leaders and have only vaguely read about this
specific area. But my guess is that the changes in carbohydrate are an
effect of transformation, which may contribute to any later changes. There
are often changes in glycosyltransferase activities after various treatments
(e.g. induction of ras oncogene with dexamethasone causes elevation of
GlcNAc transferases III and V - J. Biol. Chem. 266:21674). Very often the
N-linked oligosaccharides are more branched in tumour cells.
There are a variety of lectin molecules in eukaryotes - selectins are just
an example (sialyl Lewis X interacts with E-selectins during leukocyte
adhesion to endothelia for instance). You may be interested in a recent
paper from Ten Feizi's lab on oligosaccharide ligands in interaction of NK
cells with tumour cells - IP3 and Ca2+ changes are apparently associated
with the interaction (Nature 372:150-157).
> I apologize if these questions seem very naive; I have tried to
>search databases using terms like "carbohydrate" and "proliferation," but
>haven't come up with anything very satisfactory. I would be interested in
>discussion and speculations (even hand-waving :-)) from glycobiology
>experts, as well as references.
To date, a lot of work on carbohydrate function is 'hand-waving'. So
sometimes it's difficult to be specific. A recent book you may be interested
in is Molecular Glycobiology (Fukuda and Hindsgaul, eds., IRL Press). Then
there's a comprehensive review by Ajit Varki (Glycobiology, 3:97-130).
Perhaps we can have some discussion on these functional matters ...
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Iain Wilson Dyson Perrins Laboratory
Tel: +44-1865-275696 University of Oxford
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E-mail: iwilson at molbiol.ox.ac.uk Oxford, OX1 3QY, UK
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