Abstract
Transforming growth factor β (TGF-β) modulates a number of cellular phenotypes as divergent as growth stimulation and growth inhibition. Although the Smad pathway is critical for many of these responses, recent evidence indicates that Smad-independent pathways may also have a critical role. One such protein previously shown to regulate TGF-β action independent of the Smad proteins is the c-Abl nonreceptor tyrosine kinase. In the current study we determined that TGF-β receptor signaling activates c-Abl kinase activity in a subset of fibroblast but not epithelial cultures. This cell type-specific response occurs in a membrane-proximal locale independent of receptor internalization and upstream of dynamin action. Although c-Abl activation by TGF-β is independent of Smad2 or Smad3, it is prevented by inhibitors of phosphatidylinositol 3-kinase or PAK2. Thus, c-Abl represents a target downstream of phosphatidylinositol 3-kinase-activated PAK2, which differentiates TGF-β signaling in fibroblasts and epithelial cell lines and integrates serine/threonine receptor kinases with tyrosine kinase pathways.
Original language | English (US) |
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Pages (from-to) | 27846-27854 |
Number of pages | 9 |
Journal | Journal of Biological Chemistry |
Volume | 281 |
Issue number | 38 |
DOIs | |
State | Published - Sep 22 2006 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology