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 ◽  
...  

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.

1998 ◽  
Vol 273 (36) ◽  
pp. 23118-23125 ◽  
Author(s):  
Robert A. Anders ◽  
Jules J. E. Doré ◽  
Sandra L. Arline ◽  
Nandor Garamszegi ◽  
Edward B. Leof

2004 ◽  
Vol 15 (9) ◽  
pp. 4166-4178 ◽  
Author(s):  
Hugh Mitchell ◽  
Amit Choudhury ◽  
Richard E. Pagano ◽  
Edward B. Leof

Proteins in the transforming growth factor-β (TGF-β) family recognize transmembrane serine/threonine kinases known as type I and type II receptors. Binding of TGF-β to receptors results in receptor down-regulation and signaling. Whereas previous work has focused on activities controlling TGF-β signaling, more recent studies have begun to address the trafficking properties of TGF-β receptors. In this report, it is shown that receptors undergo recycling both in the presence and absence of ligand activation, with the rates of internalization and recycling being unaffected by ligand binding. Recycling occurs as receptors are most likely internalized through clathrin-coated pits, and then returned to the plasma membrane via a rab11-dependent, rab4-independent mechanism. Together, the results suggest a mechanism wherein activated TGF-β receptors are directed to a distinct endocytic pathway for down-regulation and clathrin-dependent degradation after one or more rounds of recycling.


1998 ◽  
Vol 18 (11) ◽  
pp. 6595-6604 ◽  
Author(s):  
Irene Griswold-Prenner ◽  
Craig Kamibayashi ◽  
E. Miko Maruoka ◽  
Marc C. Mumby ◽  
Rik Derynck

ABSTRACT We have previously shown that a WD-40 repeat protein, TRIP-1, associates with the type II transforming growth factor β (TGF-β) receptor. In this report, we show that another WD-40 repeat protein, the Bα subunit of protein phosphatase 2A, associates with the cytoplasmic domain of type I TGF-β receptors. This association depends on the kinase activity of the type I receptor, is increased by coexpression of the type II receptor, which is known to phosphorylate and activate the type I receptor, and allows the type I receptor to phosphorylate Bα. Furthermore, Bα enhances the growth inhibition activity of TGF-β in a receptor-dependent manner. Because Bα has been characterized as a regulator of phosphatase 2A activity, our observations suggest possible functional interactions between the TGF-β receptor complex and the regulation of protein phosphatase 2A.


Sign in / Sign up

Export Citation Format

Share Document