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

被引:22
作者
Kucich, U
Rosenbloom, JC
Shen, G
Abrams, WR
Blaskovich, MA
Hamilton, AD
Ohkanda, J
Sebti, SM
Rosenbloom, J [1 ]
机构
[1] Univ Penn, Sch Dent Med, Dept Anat & Histol, Philadelphia, PA 19104 USA
[2] Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Biochem & Mol Biol, Drug Discovery Program, Tampa, FL 33612 USA
[3] Yale Univ, Dept Chem, New Haven, CT 06520 USA
关键词
D O I
10.1006/bbrc.1998.9544
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The TGF-beta s 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-beta 1 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-beta 1 effect. In addition, the general tyrosine kinase inhibitor genistein completely blocked this TGF-beta 1 effect. The results suggest that the TGF-beta 1signaling pathway requires not only receptor ser/thr kinase activity, but also tyrosine kinase and small GTPase activities. (C) 1998 Acaemic Press.
引用
收藏
页码:111 / 116
页数:6
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