Post-translational modifications regulate signalling by Ror1
|Field:||Genetics and molecular biology|
|Type:||Article in Periodical|
|Keywords:||Ror1; posttranslational modifications; glycosylation; chronic lymphocytic leukemia|
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.