Cellular interactions with extracellular matrix molecules are known to be involved in may developmental, repair, and homeostatic processes, but only recently has it been established that these interactions initiate transmembrane signalling events. The most well studied pathways to date involve tyrosine phosphorylations initiated by Beta1 and Beta3 integrin receptor-ligand interactions. the adhesion of most anchorage-dependent cells in culture, and some in vivo, is characterized by structures known as focal contacts or focal adhesions. These structures are thought to be integral to wound healing processes was well as providing stable anchorage for normal cells, but are often change in structure and composition in transformed cells, where they may even be absent. They are also an excellent model for transmembrane signalling. While many focal adhesion constituents are known, the process of assembly is not understood. Both tyrosine phosphorylation and subsequent protein kinase C (PKC) activity may be involved in their formation and in this respect, the pathways resemble those for some growth factor and lymphocyte receptor interactions. The long term goal of this research is to understand the molecular events leading to the formation and maintenance of focal adhesions in primary cultured cells. It is proposed that cells forming adhesions on a fibronectin substrate utilize a dual receptor system involving both integrins and cell surface proteoglycans. The latter may promote PKC activity and the assembly of focal adhesions. The transmembrane proteoglycan involved in this process has recently been identified as a member of the syndecan family of proteoglycans.
| Thodeti, Charles Kumar; Albrechtsen, Reidar; Grauslund, Morten et al. (2003) ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through protein kinase Calpha and RhoA. J Biol Chem 278:9576-84 |
| Couchman, John R; Vogt, Susan; Lim, Ssang-Taek et al. (2002) Regulation of inositol phospholipid binding and signaling through syndecan-4. J Biol Chem 277:49296-303 |
