Chemistry Reference
In-Depth Information
11.6.1.2
Functions
Many proteins depend for their function on interaction with HS, raising the per-
spective for respective drug design. A very large number of proteins and pathogens
have been shown to interact with HS by their HS-binding region. These proteins
are protected from degradation by the presence of bound HS. Examples of the
various functions of syndecans are given in Figure 11.7 [23] .
•
The syndecans can immobilize ligands, present them to a specifi c receptor, and
prevent their degradation and contribute to the dimerization of growth factors
and/or modify their interaction with their receptor, but the syndecan action is
concentration-dependent concerning the promotion or inhibition of cell
proliferation. One example is the interaction between FGF-2 and HS that is
required for binding of FGF-2 to its high-affi nity tyrosine kinase receptor FGFR-
1. A ternary complex of growth factor, HS and receptor seems to maximize the
signaling potential of FGF-2, but an excess of free HS chains can counterbalance
the mitogenic activity of FGF- 2.
•
Syndecans are low - affi nity receptors for enzymes. They also bind lipoproteins
and can mediate uptake, lysosomal delivery and degradation of the lipoproteins
independently of specifi c lipoprotein receptors.
•
Syndecans supply attachments sites for viruses (herpes simplex virus,
Pseudorabies virus glycoprotein C and HIV-1 are bound).
•
Syndecans bind proteases and protease inhibitors. The interaction of the protease
thrombin and its inhibitor antithrombin III that controls blood coagulation is
regulated by various membrane-bound proteo-HS. Based on these fi ndings their
role in wound healing processes was the subject of many studies.
Figure 11.7
Pleiotropic functions of syndecans, adopted and extended from [23].
