Lysosomal degradation of RhoH protein upon antigen receptor activation in T but not B cells.
RhoH is a member of the Rho (ras homologous) GTPase family, yet it lacks GTPase activity and thus remains in its active conformation. Unlike other Rho GTPases, the RhoH gene transcript is restricted to hematopoietic cells and RhoH was shown to be required for adequate T-cell activation through the TCR. Here, we demonstrate that both blood T and B cells, but not neutrophils or monocytes, express RhoH protein under physiological conditions. Upon TCR complex activation, RhoH was degraded in lysosomes of primary and Jurkat T cells. Pharmacologic activation of T cells distal to the TCR complex had no effect on RhoH protein levels suggesting that early events during T-cell activation are required for RhoH protein degradation. In contrast to T cells, activation of the BCR in blood B cells was not associated with changes in RhoH levels. These data suggest that RhoH function might be regulated by lysosomal degradation of RhoH protein following TCR complex but not BCR activation. This newly discovered regulatory pathway of RhoH expression might limit TCR signaling and subsequent T-cell activation upon Ag contact.
Schmidt-Mende
Jan
J
Institute of Pharmacology, University of Bern, Bern, Switzerland.
Geering
Barbara
B
Yousefi
Shida
S
Simon
Hans-Uwe
HU
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; C447841:RhoH protein, human; D014157:Transcription Factors; D020741:rho GTP-Binding Proteins