| http://purl.uniprot.org/citations/33617900 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33617900 | http://www.w3.org/2000/01/rdf-schema#comment | "CBL is a RING type E3 ubiquitin ligase that functions as a negative regulator of tyrosine kinase signaling and loss of CBL E3 function is implicated in several forms of leukemia. The Src-like adaptor proteins (SLAP/SLAP2) bind to CBL and are required for CBL-dependent downregulation of antigen receptor, cytokine receptor, and receptor tyrosine kinase signaling. Despite the established role of SLAP/SLAP2 in regulating CBL activity, the nature of the interaction and the mechanisms involved are not known. To understand the molecular basis of the interaction between SLAP/SLAP2 and CBL, we solved the crystal structure of CBL tyrosine kinase binding domain (TKBD) in complex with SLAP2. The carboxy-terminal region of SLAP2 adopts an α-helical structure which binds in a cleft between the 4H, EF-hand, and SH2 domains of the TKBD. This SLAP2 binding site is remote from the canonical TKBD phospho-tyrosine peptide binding site but overlaps with a region important for stabilizing CBL in its autoinhibited conformation. In addition, binding of SLAP2 to CBL in vitro activates the ubiquitin ligase function of autoinhibited CBL. Disruption of the CBL/SLAP2 interface through mutagenesis demonstrated a role for this protein-protein interaction in regulation of CBL E3 ligase activity in cells. Our results reveal that SLAP2 binding to a regulatory cleft of the TKBD provides an alternative mechanism for activation of CBL ubiquitin ligase function."xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2021.166880"xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/author | "Raught B."xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/author | "Wybenga-Groot L.E."xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/author | "McGlade C.J."xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/author | "Moran M.F."xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/author | "Tench A.J."xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/author | "Simpson C.D."xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/author | "Germain J.S."xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/name | "J Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/pages | "166880"xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/title | "SLAP2 Adaptor Binding Disrupts c-CBL Autoinhibition to Activate Ubiquitin Ligase Function."xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://purl.uniprot.org/core/volume | "433"xsd:string |
| http://purl.uniprot.org/citations/33617900 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33617900 |
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