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FYN and ABL Regulate the Interaction Networks of the DCBLD Receptor Family

Anna M Schmoker1, Jaye L Weinert1, Jacob M Markwood2

  • 1Department of Biology, University of Vermont, Marsh Life Sciences, Burlington, Vermont, USA.

Molecular & Cellular Proteomics : MCP
|July 2, 2020
PubMed

Insights

Discoidin, CUB, and LCCL domain-containing proteins (DCBLD) interact with new signaling molecules beyond CRK/CRKL. FYN and ABL kinases regulate these interactions, including binding to 14-3-3 adaptors, impacting cellular signaling pathways.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Cancer research

Background:

  • Discoidin, CUB, and LCCL domain-containing protein (DCBLD) family members are type-I transmembrane scaffolding receptors crucial for development and cancer.
  • FYN and ABL kinases phosphorylate DCBLD proteins, recruiting CRK and CRK-like (CRKL) adaptors via SH2 domains.
  • Previous work focused on FYN/ABL-driven phosphorylation of YXXP motifs, but additional sites exist.

Purpose of the Study:

  • To identify novel FYN- and ABL-regulated interactors of DCBLD1 and DCBLD2.
  • To explore the functional consequences of these new interactions in cellular signaling.

Main Methods:

  • Quantitative proteomics to map FYN- and ABL-regulated interactomes of DCBLD family members.
  • Biochemical assays to validate specific protein-protein interactions.

Main Results:

  • FYN and ABL kinases regulate the binding of multiple signaling molecules to DCBLD1 and DCBLD2.
  • 14-3-3 family members were identified as novel DCBLD interactors regulated by FYN and ABL.
  • ABL kinase directly induces the binding of 14-3-3 proteins to DCBLD2.

Conclusions:

  • FYN and ABL kinases modulate DCBLD1 and DCBLD2 interactions with a broader range of signaling proteins than previously known.
  • The interaction with 14-3-3 adaptors represents a new regulatory mechanism for DCBLD proteins, potentially impacting cancer and development.
Keywords:
14-3-3ABLDCBLDESDNFYNPhosphorylationSILAClabel-free quantificationmass spectrometryprotein-protein interactions

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