FYN and ABL Regulate the Interaction Networks of the DCBLD Receptor Family
| Autor: | Bryan A. Ballif, Karen L. Hinkle, Jaye L. Weinert, Kathryn S. Albretsen, Anna M. Schmoker, Jacob M. Markwood, Michelle L. Lunde, Marion E. Weir, Alicia M. Ebert |
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| Rok vydání: | 2020 |
| Předmět: |
Phosphopeptides
ABL protein-protein interactions Biology Proto-Oncogene Proteins c-fyn Biochemistry Models Biological SILAC label-free quantification Analytical Chemistry 03 medical and health sciences Adapter molecule crk FYN Humans Amino Acid Sequence Protein Interaction Maps Phosphorylation Proto-Oncogene Proteins c-abl Molecular Biology 14-3-3 030304 developmental biology mass spectrometry 0303 health sciences Kinase Research 030302 biochemistry & molecular biology Membrane Proteins Cell biology CRKL enzymes and coenzymes (carbohydrates) HEK293 Cells ESDN embryonic structures DCBLD Tyrosine kinase Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Molecular & Cellular Proteomics : MCP |
| ISSN: | 1535-9484 |
| Popis: | The FYN- and ABL-regulated interactomes of DCBLD proteins have been determined using quantitative mass spectrometry-based proteomics. FYN and ABL drove the binding of several signaling molecules to DCBLD1 and DCBLD2, including members of the 14-3-3 family of adaptors. Biochemical investigation of the DCBLD2/14-3-3 interaction revealed ABL-induced binding of 14-3-3 family members directly to DCBLD2.The interactions identified in this screen present important steps in elucidating signaling events involving DCBLD proteins in developmental and oncogenic signaling. Graphical Abstract Highlights • FYN and ABL differentially regulate DCBLD Ser/Thr/Tyr phosphorylation. • DCBLD1 and DCBLD2 interactomes are modulated by FYN and ABL. • ABL drives a direct DCBLD2/14-3-3 interaction. The Discoidin, CUB, and LCCL domain-containing protein (DCBLD) family consists of two type-I transmembrane scaffolding receptors, DCBLD1 and DCBLD2, which play important roles in development and cancer. The nonreceptor tyrosine kinases FYN and ABL are known to drive phosphorylation of tyrosine residues in YXXP motifs within the intracellular domains of DCBLD family members, which leads to the recruitment of the Src homology 2 (SH2) domain of the adaptors CT10 regulator of kinase (CRK) and CRK-like (CRKL). We previously characterized the FYN- and ABL-driven phosphorylation of DCBLD family YXXP motifs. However, we have identified additional FYN- and ABL-dependent phosphorylation sites on DCBLD1 and DCBLD2. This suggests that beyond CRK and CRKL, additional DCBLD interactors may be regulated by FYN and ABL activity. Here, we report a quantitative proteomics approach in which we map the FYN- and ABL-regulated interactomes of DCBLD family members. We found FYN and ABL regulated the binding of several signaling molecules to DCBLD1 and DCBLD2, including members of the 14-3-3 family of adaptors. Biochemical investigation of the DCBLD2/14-3-3 interaction revealed ABL-induced binding of 14-3-3 family members directly to DCBLD2. |
| Databáze: | OpenAIRE |
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