scholarly journals Differential Requirement for Type I and Type II Transforming Growth Factor β Receptor Kinase Activity in Ligand-mediated Receptor Endocytosis

1998 ◽  
Vol 273 (36) ◽  
pp. 23118-23125 ◽  
Author(s):  
Robert A. Anders ◽  
Jules J. E. Doré ◽  
Sandra L. Arline ◽  
Nandor Garamszegi ◽  
Edward B. Leof
Keyword(s):  
Growth Factor ◽  
Kinase Activity ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Type Ii ◽  
Receptor Kinase ◽  
Receptor Endocytosis ◽  
Β Receptor

scholarly journals Type II Transforming Growth Factor-β Receptor Recycling Is Dependent upon the Clathrin Adaptor Protein Dab2

2010 ◽  
Vol 21 (22) ◽  
pp. 4009-4019 ◽  
Author(s):  
Sumedha G. Penheiter ◽  
Raman Deep Singh ◽  
Claire E. Repellin ◽  
Mark C. Wilkes ◽  
Maryanne Edens ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Density Lipoprotein ◽  
Adaptor Protein ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Type Ii ◽  
Receptor Recycling ◽  
Smad2 Phosphorylation ◽  
Β Receptor

Transforming growth factor (TGF)-β family proteins form heteromeric complexes with transmembrane serine/threonine kinases referred to as type I and type II receptors. Ligand binding initiates a signaling cascade that generates a variety of cell type-specific phenotypes. Whereas numerous studies have investigated the regulatory activities controlling TGF-β signaling, there is relatively little information addressing the endocytic and trafficking itinerary of TGF-β receptor subunits. In the current study we have investigated the role of the clathrin-associated sorting protein Disabled-2 (Dab2) in TGF-β receptor endocytosis. Although small interfering RNA-mediated Dab2 knockdown had no affect on the internalization of various clathrin-dependent (i.e., TGF-β, low-density lipoprotein, or transferrin) or -independent (i.e., LacCer) cargo, TGF-β receptor recycling was abrogated. Loss of Dab2 resulted in enlarged early endosomal antigen 1-positive endosomes, reflecting the inability of cargo to traffic from the early endosome to the endosomal recycling compartment and, as documented previously, diminished Smad2 phosphorylation. The results support a model whereby Dab2 acts as a multifunctional adaptor in mesenchymal cells required for TGF-β receptor recycling as well as Smad2 phosphorylation.

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