Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration - PubMed (original) (raw)
. 1999 Oct 22;274(43):30896-905.
doi: 10.1074/jbc.274.43.30896.
Affiliations
- PMID: 10521483
- DOI: 10.1074/jbc.274.43.30896
Free article
Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration
N Jones et al. J Biol Chem. 1999.
Free article
Abstract
The Tek/Tie2 receptor tyrosine kinase plays a pivotal role in vascular and hematopoietic development. To study the signal transduction pathways that are mediated by this receptor, we have used the yeast two-hybrid system to identify signaling molecules that associate with the phosphorylated Tek receptor. Using this approach, we demonstrate that five molecules, Grb2, Grb7, Grb14, Shp2, and the p85 subunit of phosphatidylinositol 3-kinase can interact with Tek in a phosphotyrosine-dependent manner through their SH2 domains. Mapping of the binding sites of these molecules on Tek reveals the presence of a multisubstrate docking site in the carboxyl tail of Tek (Tyr(1100)). Mutation of this site abrogates binding of Grb2 and Grb7 to Tek in vivo, and this site is required for tyrosine phosphorylation of Grb7 and p85 in vivo. Furthermore, stimulation of Tek-expressing cells with Angiopoietin-1 results in phosphorylation of both Tek and p85 and in activation of endothelial cell migration and survival pathways that are dependent in part on phosphatidylinositol 3-kinase. Taken together, these results demonstrate that Angiopoietin-1-induced signaling from the Tek receptor is mediated by a multifunctional docking site that is responsible for activation of both cell migration and cell survival pathways.
Similar articles
- FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors.
Ong SH, Guy GR, Hadari YR, Laks S, Gotoh N, Schlessinger J, Lax I. Ong SH, et al. Mol Cell Biol. 2000 Feb;20(3):979-89. doi: 10.1128/MCB.20.3.979-989.2000. Mol Cell Biol. 2000. PMID: 10629055 Free PMC article. - Grb10 is a dual regulator of receptor tyrosine kinase signaling.
Kabir NN, Kazi JU. Kabir NN, et al. Mol Biol Rep. 2014;41(4):1985-92. doi: 10.1007/s11033-014-3046-4. Epub 2014 Jan 14. Mol Biol Rep. 2014. PMID: 24420853 Review. - Inhibitory receptors abound?
Cambier JC. Cambier JC. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):5993-5. doi: 10.1073/pnas.94.12.5993. Proc Natl Acad Sci U S A. 1997. PMID: 9177155 Free PMC article. Review. No abstract available.
Cited by
- GRB7-mediated enhancement of cell malignant characteristics induced by Helicobacter pylori infection.
Zhao H, Chen S, Bai X, Zhang J, Liu S, Sun Z, Cao X, Wang J, Zhang Y, Li B, Ji X. Zhao H, et al. Front Microbiol. 2024 Sep 18;15:1469953. doi: 10.3389/fmicb.2024.1469953. eCollection 2024. Front Microbiol. 2024. PMID: 39360313 Free PMC article. - Human iPSC and CRISPR targeted gene knock-in strategy for studying the somatic TIE2L914F mutation in endothelial cells.
Lazovic B, Nguyen HT, Ansarizadeh M, Wigge L, Kohl F, Li S, Carracedo M, Kettunen J, Krimpenfort L, Elgendy R, Richter K, De Silva L, Bilican B, Singh P, Saxena P, Jakobsson L, Hong X, Eklund L, Hicks R. Lazovic B, et al. Angiogenesis. 2024 Aug;27(3):523-542. doi: 10.1007/s10456-024-09925-9. Epub 2024 May 21. Angiogenesis. 2024. PMID: 38771392 Free PMC article. - Anti-angiogenesis in colorectal cancer therapy.
Yang Z, Zhang X, Bai X, Xi X, Liu W, Zhong W. Yang Z, et al. Cancer Sci. 2024 Mar;115(3):734-751. doi: 10.1111/cas.16063. Epub 2024 Jan 17. Cancer Sci. 2024. PMID: 38233340 Free PMC article. Review. - A novel implant surface modification mode of Fe3O4-containing TiO2 nanorods with sinusoidal electromagnetic field for osteoblastogenesis and angiogenesis.
Ren R, Guo J, Song H, Wei Y, Luo C, Zhang Y, Chen L, Gao B, Fu J, Xiong W. Ren R, et al. Mater Today Bio. 2023 Feb 22;19:100590. doi: 10.1016/j.mtbio.2023.100590. eCollection 2023 Apr. Mater Today Bio. 2023. PMID: 36910272 Free PMC article. - Novel Drugs with High Efficacy against Tumor Angiogenesis.
Qi S, Deng S, Lian Z, Yu K. Qi S, et al. Int J Mol Sci. 2022 Jun 22;23(13):6934. doi: 10.3390/ijms23136934. Int J Mol Sci. 2022. PMID: 35805939 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous