The long-range objective of this project is to determine the functional significance of the multiple heparin sulfate chains on proteoglycans. Each chain may contribute to the optimal activity of the molecule. Alternatively, each chain may be required for a distinct function. The heparin sulfate chains of syndecan-1 are biologically active in mediating cell:substratum and cell:cell adhesion and in inhibiting cell invasion. To test the hypothesis that all three of the highly conserved heparin sulfate attachment sites are required for maximal biological activity, in specific aim 1, a panel of syndecan- 1 glycosaminoglycan deletion mutants will be prepared using oligonucleotide-directed mutagenesis.
In specific aim 2, myeloma cells transfected with the various mutated syndecan-1 cDNAs will be examined in functional assays to determine how alterations in glycosaminoglycan composition affect: (i) cell:substratum adhesion.
| Dhodapkar, M V; Abe, E; Theus, A et al. (1998) Syndecan-1 is a multifunctional regulator of myeloma pathobiology: control of tumor cell survival, growth, and bone cell differentiation. Blood 91:2679-88 |
| Langford, J K; Stanley, M J; Cao, D et al. (1998) Multiple heparan sulfate chains are required for optimal syndecan-1 function. J Biol Chem 273:29965-71 |
