c-Cbl mediated ubiquitylation and regulation of cell surface exposure of CD5.
Downregulation of cell surface receptors is an important process aimed at attenuation or termination of receptor signaling. c-Cbl role in the process is thought to be initial ubiquitylation of the receptors targeted for degradation and assembly of internalization complexes consisting of several other proteins. c-Cbl seems to be present during the whole process of vesicle sorting after internalization. However, there are very few receptor molecules so far like EGFR being proven to be regulated by c-Cbl. It is known that a level of CD5 on mouse c-Cbl-/- thymocytes is upregulated in comparison to wild type cells. The mechanism leading to the upregulation is unknown. We show that CD5 is ubiquitylated in Jurkat-TAg cells and in mouse thymocytes and that the ubiquitylation is c-Cbl dependent. We also show that amount of CD5 associated with lysosomal marker LAMP-1 after stimulation is significantly lower in c-Cbl-/- thymocytes. CD5 mRNA level did not differ significantly between c-Cbl-/- and wild type thymocytes. We conclude that CD5 is ubiquitylated; the ubiquitylation is mediated by c-Cbl; CD5 level on a T lymphocyte cell surface is regulated by ubiquitylation and targeting to lysosomes.
Demydenko
Dmytro
D
La Jolla Institute for Allergy & Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA. d.v.demydenko@gmail.com
D000818:Animals; D018956:CD5 Antigens / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D019169:Jurkat Cells; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D054875:Ubiquitination; D052118:Lysosomal-Associated Membrane Protein 1
D018956:CD5 Antigens; D051907:Lysosomal Membrane Proteins; D050721:Proto-Oncogene Proteins c-cbl; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1