Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Src homology 2 domain containing protein 5 (SH2D5) binds the breakpoint cluster region protein, BCR, and regulates levels of Rac1-GTP

[img]
Preview
PDF (Original article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
4MB

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. and Petsalaki, E. and James, D.A. and Bagshaw, R.D. and Stacey, M.M. and Rocks, O. and 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 (U.S.A.)
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

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library