Abstract
Signaling through receptor tyrosine kinases (RTKs) is implicated in the control of various cellular functions. Immediately after activation, these RTKs are rapidly translocated from cell surface into the endosomal compartment. Then, these are sorted into lysosomes for degradation. We have previously shown that degradation of EGF receptor (EGFR) is controlled by ubiquitination of activated EGFR and CIN85 by Cbl, a RING-type E3 ubiquitin ligase. On the other hand, TrkA, a member of RTK family, is also internalized after activation by NGF and targeted for degradation. Here we report that the TrkA are ubiquitinated in response to NGF. The ubiquitination of TrkA is induced by Nedd4-2, HECT-type E3 ubiquitin ligases. We also found that Cbl promotes degradation of activated TrkA through ubiquitination. Our data provide that Nedd4-2 and Cbl promote the downregulation of TrkA through ubiquitination. [J Physiol Sci. 2008;58 Suppl:S85]
