Post-translational modifications regulate signalling by Ror1
| Authors | |
|---|---|
| Year of publication | 2011 |
| Type | Article in Periodical |
| Magazine / Source | Acta Physiologica |
| MU Faculty or unit | |
| Citation | |
| Doi | http://dx.doi.org/10.1111/j.1748-1716.2011.02306.x |
| Field | Genetics and molecular biology |
| Keywords | Ror1; posttranslational modifications; glycosylation; chronic lymphocytic leukemia |
| Description | Ror1 (receptor tyrosine kinase-like orphan receptor)is highly upregulated in B cells of patients with chronic lymphocytic leukaemia (CLL). Ror1 acts as the Wnt receptor in the non-canonical Wnt pathway. We demonstrate that Ror1 is extensively modified by N-linked glycosylation. Glycosylation produces several variants of Ror1 with electrophoretic migration of approx. 100, 115 and 130 kDa. Inhibition of glycosylation interferes with cell surface localization of the 130-kDa variant of Ror1 and prevents Ror1-induced formation of filopodia. Moreover, we show that 130-kDa Ror1 is mono-ubiquitinated. Furthermore, individual CLL patients show striking differences in the electrophoretic migration of Ror1, which correspond to the level of glycosylation. Our data show that Ror1 undergoes complex post-translational modifications by glycosylation and mono-ubiquitination. These modifications regulate Ror1 localization and signalling, and are highly variable among individual CLL patients. These may suggest that Ror1 signals only in a subset of CLL patients despite Ror1 levels are ubiquitously high in all CLL patients. |
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