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| Item Type: | Article |
|---|---|
| Title: | Src homology 2 domain containing protein 5 (SH2D5) binds the breakpoint cluster region protein, BCR, and regulates levels of Rac1-GTP |
| Creators Name: | Gray, E.J., Petsalaki, E., James, D.A., Bagshaw, R.D., Stacey, M.M., Rocks, O., Gingras, A.C. and Pawson, T. |
| Abstract: | SH2D5 is a mammalian-specific, uncharacterized adaptor-like protein that contains an N-terminal phosphotyrosine binding (PTB) domain and a C-terminal Src Homology 2 (SH2) domain. We show that SH2D5 is highly enriched in adult mouse brain, particularly in purkinjie cells in the cerebellum and the cornu ammonis of the hippocampus. Despite harboring two potential phosphotyrosine (pTyr) recognition domains, SH2D5 binds minimally to pTyr ligands, consistent with the absence of a conserved pTyr-binding arginine residue in the SH2 domain. Immunoprecipitation coupled to mass spectrometry (IP-MS) from cultured cells revealed a prominent association of SH2D5 with Breakpoint Cluster Region protein (BCR), a RacGAP that is also highly expressed in brain. This interaction occurred between the PTB domain of SH2D5 and an NxxF motif located within the N-terminal region of BCR. siRNA-mediated depletion of SH2D5 in a neuroblastoma cell line, B35, induced a cell rounding phenotype correlated with low levels of activated Rac1-GTP, suggesting that SH2D5 affects Rac1-GTP levels. Taken together, our data provide the first characterization of the SH2D5 signaling protein. |
| Keywords: | Mass Spectrometry (MS), Phosphotyrosine, Ras-Related C3 Botulinum Toxin Substrate 1 (Rac1), Signal Transduction, Src Homology 2 Domain (SH2 Domain), BCR Signaling, PTB Domain, Rho GTPases, SH2D5 Signaling, Adaptor Proteins, Animals, Mice, Rats |
| Source: | Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Volume: | 289 |
| Number: | 51 |
| Page Range: | 35397-35408 |
| Date: | 19 December 2014 |
| Official Publication: | https://doi.org/10.1074/jbc.M114.615112 |
| PubMed: | View item in PubMed |
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