Aston Research Explorer
Wang, Zhuo; Telci, Dilek and Griffin, Martin (2011). Importance of syndecan-4 and syndecan -2 in osteoblast cell adhesion and survival mediated by a tissue transglutaminase-fibronectin complex. Experimental cell research, 317 (3), pp. 367-381.
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Tissue transglutaminase (TG2) has been identified as an important extracellular crosslinking enzyme involved in matrix turnover and in bone differentiation. Here we report a novel cell adhesion/survival mechanism in human osteoblasts (HOB) which requires association of FN bound TG2 with the cell surface heparan sulphates in a transamidase independent manner. This novel pathway not only enhances cell adhesion on FN but also mediates cell adhesion and survival in the presence of integrin competing RGD peptides. We investigate the involvement of cell surface receptors and their intracellular signalling molecules to further explore the pathway mediated by this novel TG-FN heterocomplex. We demonstrate by siRNA silencing the crucial importance of the cell surface heparan sulphate proteoglycans syndecan-2 and syndecan-4 in regulating the compensatory effect of TG-FN on osteoblast cell adhesion and actin cytoskeletal formation in the presence of RGD peptides. By use of immunoprecipitation and inhibitory peptides we show that syndecan-4 interacts with TG2 and demonstrate that syndecan-2 and the a5ß1 integrins, but not a4ß1 function as downstream modulators in this pathway. Using function blocking antibodies, we show activation of a5ß1 occurs by an inside out signalling mechanism involving activation and binding of protein kinase PKCa and phosphorylation of focal adhesion kinase (FAK) at Tyr861 and activation of ERK1/2.
|Additional Information:||MEDLINE® is the source for the MeSH terms of this document.|
|Uncontrolled Keywords:||tissue transglutaminase, osteoblasts, integrin, syndecan, cell adhesion|
|Divisions:||Schools_of_Study > Life & Health Sciences > Biosciences (LHS)|
Schools_of_Study > Life & Health Sciences > Pharmacy (LHS)
Support_Departments > Senior Pro-Vice-Chancellor > PVC (Research) > PVC's Office (Res)
|Deposited By:||Prof Alfred Admin|
|Deposited On:||10 Dec 2012 15:36|
|Last Modified:||25 Sep 2014 09:00|
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