Intracellular trafficking of transforming growth factor beta receptors

• Transforming growth factor beta (TGF beta) family members signal via heterotetrameric complexes of type I (T beta RI) and type II (T beta RII) dual specificity kinase receptors. The availability of the receptors on the cell surface is controlled by several mechanisms. Newly synthesized T beta RI and T beta RII are delivered from the Golgi apparatus to the cell surface via separate routes. On the cell surface, TGF beta receptors are distributed between different microdomains of the plasma membrane and can be internalized via clathrin- and caveolae-mediated endocytic mechanisms. Although receptor endocytosis is not essential for TGF beta signaling, localization of the activated receptor complexes on the early endosomes promotes TGF beta-induced Smad activation. Caveolae-mediated endocytosis, which is widely regarded as a mechanism that facilitates the degradation of TGF beta receptors, has been shown to be required for TGF beta signaling via non-Smad pathways. The importance of proper control of TGF beta receptor intracellular trafficking is emphasized by clinical data, as mislocalization of receptors has been described in connection with several human diseases. Thus, control of intracellular trafficking of the TGF beta receptors together with the regulation of their expression, posttranslational modifications and down-regulation, ensure proper regulation of TGF beta signaling.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

TGF beta receptor

endocytosis

clathrin

lipid rafts

endosome

Publikations- och innehållstyp

ref (ämneskategori)

for (ämneskategori)