Mechanisms of Regulatory Pathways for Stromelysin-1 Matrix metalloproteinases (MMPs) are a family of enzymes involved in the degradation of multiple extracellular matrix (ECM) components such as gelatin, collagens, elastin, fibronectin, and laminin. Increased levels of MMP-3 (stromelysin-1) have been observed in disease processes such as arthritis and metastatic cancers. Recently investigators has demonstrated that the expression of stromelysin can be regulated by ligand-receptor interactions of the fibronectin receptor, alpha5Beta1 integrin. The phosphorylation of a focal-contact associated tyrosine kinase (p125fak) has been shown to be involved with integrin signaling of the fibronectin receptor. The conditions of integrin-ligand interaction which are associated with a decrease in phosphorylation of P125fak are conditions that are associated with an increase in the expression of mRNA for stromelysin-1. These observations suggested that the mechanism for regulation of stromelysin mRNA mediated by the fibronectin receptor may involve a decrease in the phosphorylation of p125fak.
Specific Aim #1. Deletion and mutation CAT constructs of the stromelysin promoter, already development by other investigators, will be used to determine the region of the promoter involved in the integrin mediated regulation of stromelysin.
Specific Aim #2. Correlation between the activation of the promoter region defined in specific aim #1 and the decrease in phosphorylation of p125fak will be investigated using immunoprecipitation techniques.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
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University of Texas Health Science Center San Antonio
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Lyles, Mark B; Cameron, Ivan L (2002) Caffeine and other xanthines as cytochemical blockers and removers of heterocyclic DNA intercalators from chromatin. Cell Biol Int 26:145-54
Lyles, Mark B; Cameron, Ivan L (2002) Interactions of the DNA intercalator acridine orange, with itself, with caffeine, and with double stranded DNA. Biophys Chem 96:53-76
Lyles, M B; Cameron, I L; Rawls, H R (2001) Structural basis for the binding affinity of xanthines with the DNA intercalator acridine orange. J Med Chem 44:4650-60
Flynn, M A; Qiao, M; Garcia, C et al. (1999) Avian osteoclast cells are stimulated to resorb calcified matrices by and possess receptors for leukotriene B4. Calcif Tissue Int 64:154-9
Dongari-Bagtzoglou, A I; Ebersole, J L (1998) Increased presence of interleukin-6 (IL-6) and IL-8 secreting fibroblast subpopulations in adult periodontitis. J Periodontol 69:899-910
Novak, K F; Lee, L N; LeBlanc, D J (1998) Functional analysis of pVT745, a plasmid from Actinobacillus actinomycetemcomitans. Oral Microbiol Immunol 13:124-8
Dongari-Bagtzoglou, A I; Warren, W D; Berton, M T et al. (1997) CD40 expression by gingival fibroblasts: correlation of phenotype with function. Int Immunol 9:1233-41
Klebe, R J; Grant, G M; Grant, A M et al. (1996) RT-PCR without RNA isolation. Biotechniques 21:1094-100
Hill, S J; Ebersole, J L (1996) The effect of lipopolysaccharide on growth factor-induced mitogenesis in human gingival fibroblasts. J Periodontol 67:1274-80
Dongari-Bagtzoglou, A I; Ebersole, J L (1996) Gingival fibroblast cytokine profiles in Actinobacillus actinomycetemcomitans-associated periodontitis. J Periodontol 67:871-8

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