TY - JOUR
T1 - Requirement for geranylgeranyl transferase I and acyl transferase in the TGF-β-stimulated pathway leading to elastin mRNA stabilization
AU - Kucich, Umberto
AU - Rosenbloom, Joan C.
AU - Shen, Gloria
AU - Abrams, William R.
AU - Blaskovich, Michelle A.
AU - Hamilton, Andrew D.
AU - Ohkanda, Junko
AU - Sebti, Saïd M.
AU - Rosenbloom, Joel
N1 - Funding Information:
This work was supported by National Institutes of Health Grants HL56401 (J.R.) and CA67771 (S.M.S. and A.D.H.).
PY - 1998/11/9
Y1 - 1998/11/9
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1998.9544
DO - 10.1006/bbrc.1998.9544
M3 - Article
C2 - 9813154
AN - SCOPUS:0032501165
SN - 0006-291X
VL - 252
SP - 111
EP - 116
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -