Requirement for geranylgeranyl transferase I and acyl transferase in the TGF-β-stimulated pathway leading to elastin mRNA stabilization

The TGF-βs are multipotent in their biological activity, modulating cell growth and differentiation as well as extracellular matrix deposition and degradation. Most of these activities involve modulation of gene transcription. However, TGF-β1 has been shown previously to substantially increase the expression of elastin by stabilization of tropoelastin mRNA through a signaling pathway which involves a phosphatidylcholine-specific phospholipase and a protein kinase C. The present results, through the use of specific inhibitors of geranylgeranyl transferase I, farnesyl transferase, and acyl transferase, demonstrate that geranylgeranylated and acylated, but not farnesyslated protein(s) is required for this TGF-β1 effect. In addition, the general tyrosine kinase inhibitor genistein completely blocked this TGF-β1 effect. The results suggest that the TGF-β1 signaling pathway requires not only receptor ser/thr kinase activity, but also tyrosine kinase and small GTPase activities.