| http://purl.uniprot.org/citations/24509848 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24509848 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24509848 | http://www.w3.org/2000/01/rdf-schema#comment | "Discoidin domain receptor 1 (DDR1) belongs to a unique family of receptor tyrosine kinases that signal in response to collagens. DDR1 undergoes autophosphorylation in response to collagen binding with a slow and sustained kinetics that is unique among members of the receptor tyrosine kinase family. DDR1 dimerization precedes receptor activation suggesting a structural inhibitory mechanism to prevent unwarranted phosphorylation. However, the mechanism(s) that maintains the autoinhibitory state of the DDR1 dimers is unknown. Here, we report that N-glycosylation at the Asn(211) residue plays a unique role in the control of DDR1 dimerization and autophosphorylation. Using site-directed mutagenesis, we found that mutations that disrupt the conserved (211)NDS N-glycosylation motif, but not other N-glycosylation sites (Asn(260), Asn(371), and Asn(394)), result in collagen I-independent constitutive phosphorylation. Mass spectrometry revealed that the N211Q mutant undergoes phosphorylation at Tyr(484), Tyr(520), Tyr(792), and Tyr(797). The N211Q traffics to the cell surface, and its ectodomain displays collagen I binding with an affinity similar to that of the wild-type DDR1 ectodomain. However, unlike the wild-type receptor, the N211Q mutant exhibits enhanced receptor dimerization and sustained activation upon ligand withdrawal. Taken together, these data suggest that N-glycosylation at the highly conserved (211)NDS motif evolved to act as a negative repressor of DDR1 phosphorylation in the absence of ligand. The presence of glycan moieties at that site may help to lock the collagen-binding domain in the inactive state and prevent unwarranted signaling by receptor dimers. These studies provide a novel insight into the structural mechanisms that regulate DDR activation."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.541102"xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.541102"xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Huang P."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Huang P."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Fu H.L."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Fu H.L."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Mobashery S."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Mobashery S."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Kumarasiri M."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Kumarasiri M."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Payne L."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Payne L."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Fridman R."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Fridman R."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Mahasenan K.V."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Mahasenan K.V."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Valiathan R.R."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/author | "Valiathan R.R."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/24509848 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |