GAG contributions to receptor function

PJOB obrien at pharm.med.upenn.edu
Mon Dec 12 16:56:25 EST 1994

Someone, somewhere, recently said:

> Also,
> I just wanted to remark to Dr. Jefferis on his 'functional aspect of
> glycosylation of receptors' question.  I'm not sure how 'functional' this
> is, but certainly receptors (their binding sites, that is) must extend out
> from the cell surface to do their job, and this means getting through the
> jungle of carbohydrates which dominate (as we know) the surface.  Extensive
> studies (sorry, no references on me, but you know you can look up Brown and
> Goldstein on Medline--you use Medline in the U.K. also?) of the LDL-receptor
> O-glycosylation indicates (I believe) an important role for maintaining
> rigidity of the 'stalk' portion of the molecule which spaces out the part of
> the molecule responsible for binding away from the cell surface.  Is that
> functional enough for you?  (conclusion from studies w/ glycosylation
> inhibitors in a cell culture expression system, if memory serves correctly)
> I hope this off-the-cuff immediate answer (without having first checked the
> refs.) is acceptable.

I don't know if this example is valid to the discussion at hand (since it
involves GAG chains) but here are some relevant refs from the Hematology
front that might apply...

Recombinant human thrombomodulin. Regulation of cofactor activity and
anticoagulant function by a glycosaminoglycan side chain. Biochem J. 1992
Apr 1; 283 ( Pt 1): 151-7.

Relationship between post-translational glycosylation and anticoagulant
function of secretable recombinant mutants of human thrombomodulin. Br J
Haematol. 1991 Aug; 78(4): 515-22.
Role of the glycosaminoglycan component of thrombomodulin in its
acceleration of the inactivation of single-chain urokinase-type plasminogen
activator by thrombin. Biochem J. 1993 Mar 15; 290 ( Pt 3): 655-9.

Thrombomodulin: an anticoagulant cell surface proteoglycan with
physiologically relevant glycosaminoglycan moiety. Adv Exp Med Biol. 1992;
313: 177-88.


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