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Structural requirements for cub domain containing protein 1 (CDCP1) and Src dependent cell transformation
Gwendlyn Kollmorgen1, Birgit Bossenmaier, Gerhard Niederfellner
1Pharma Research and Early Development, Roche Diagnostics GmbH, Penzberg, Germany.
Plos One
|January 10, 2013
Summary
Cub domain containing protein 1 (CDCP1) and Src kinase co-overexpression drives cellular transformation. Intact CDCP1 termini and specific tyrosine residues are crucial for this transformation, highlighting key structural requirements.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Cub domain containing protein 1 (CDCP1) is upregulated in various cancers, including lung, colon, ovarian, and kidney tumors.
- CDCP1 is a membrane protein interacting with Src family kinases, but its role in cellular transformation requires further elucidation.
- Existing research lacks experimental systems to fully evaluate CDCP1's transformation-driving features.
Purpose of the Study:
- To define the structural requirements of CDCP1 and Src in cellular transformation.
- To investigate the specific domains and residues of CDCP1 essential for transformation.
- To characterize the interaction between CDCP1 and Src kinase in the context of cell transformation.
Main Methods:
- Retrovirus-mediated co-overexpression of c-Src and CDCP1 in NIH3T3 cells to induce focus formation.
- Utilized various CDCP1 mutants to assess the impact of specific structural features on transformation capacity.
- Employed Src mutants to investigate the role of Src kinase domains and modifications in CDCP1-dependent transformation.
Main Results:
- Full transformation capacity of CDCP1 requires intact amino- and carboxy-termini.
- Mutation of core intracellular tyrosine residues (Y734, Y743, Y762) abolished transformation.
- Mutation of the palmitoylation motif (C689,690G) significantly reduced transformation, while Src SH2 domain mutation enhanced CDCP1-dependent foci.
Conclusions:
- The focus formation assay effectively defines structural requirements for CDCP1/Src-dependent transformation.
- Specific intracellular tyrosine residues and intact termini of CDCP1 are critical for its oncogenic function.
- Src kinase myristoylation is necessary, but SH2 domain binding is not essential for CDCP1-mediated transformation.
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