Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM domain interactions
Affiliation
Univ Arizona, Ctr Biomed Informat & BiostatIssue Date
2018-05-11
Metadata
Show full item recordPublisher
ELIFE SCIENCES PUBLICATIONS LTDCitation
eLife 2018;7:e35677Journal
ELIFERights
© 2018, Wang et al. This article is distributed under the terms of the Creative Commons Attribution License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
The Eph receptor tyrosine kinase (RTK) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning, neurogenesis and neuronal circuit formation, angiogenesis, etc. How the 14 Eph proteins, via their highly similar cytoplasmic domains, can transmit diverse and sometimes opposite cellular signals upon engaging ephrins is a major unresolved question. Here, we systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM SAM interaction-mediated cytoplasmic Eph-effector binding pattern. Comparative X-ray crystallographic studies of several SAM SAM heterodimer complexes, together with biochemical and cell biology experiments, not only revealed the exquisite specificity code governing Eph/effector interactions but also allowed us to identify SAMD5 as a new Eph binding partner. Finally, these Eph/effector SAM heterodimer structures can explain many Eph SAM mutations identified in patients suffering from cancers and other diseases.Note
Open Access Journal*/Paid Open Access after January 2017*ISSN
2050-084XPubMed ID
29749928DOI
10.7554/eLife.3567710.7554/eLife.35677.001
10.7554/eLife.35677.002
10.7554/eLife.35677.003
10.7554/eLife.35677.004
10.7554/eLife.35677.005
10.7554/eLife.35677.006
10.7554/eLife.35677.007
10.7554/eLife.35677.008
10.7554/eLife.35677.009
10.7554/eLife.35677.010
10.7554/eLife.35677.011
10.7554/eLife.35677.012
10.7554/eLife.35677.013
10.7554/eLife.35677.014
10.7554/eLife.35677.015
10.7554/eLife.35677.016
10.7554/eLife.35677.017
10.7554/eLife.35677.029
10.7554/eLife.35677.030
10.7554/eLife.35677.019
10.7554/eLife.35677.020
Version
Final published versionSponsors
Ministry of Science and Technology [2014CB910204, 2016YFA0501903]; Natural Science Foundation of Guangdong Province [2016A030312016]; Shenzhen Basic Research Grant, Shenzhen, China [JCYJ20160229153100269, JCYJ20160427185712266, JCYJ20170411090807530]; National Natural Science Foundation of China [31670765]; Asia Fund for Cancer Research [AFCR17SC01]Additional Links
https://elifesciences.org/articles/35677https://elifesciences.org/articles/35677#abstract
https://elifesciences.org/articles/35677#digest
https://elifesciences.org/articles/35677#fig1
https://elifesciences.org/articles/35677#table1
https://elifesciences.org/articles/35677#fig2
https://elifesciences.org/articles/35677/figures#fig2s1
https://elifesciences.org/articles/35677/figures#fig2s2
https://elifesciences.org/articles/35677/figures#fig2s3
https://elifesciences.org/articles/35677/figures#fig2s4
https://elifesciences.org/articles/35677/figures#fig2s5
https://elifesciences.org/articles/35677#fig3
https://elifesciences.org/articles/35677/figures#fig3s1
https://elifesciences.org/articles/35677/figures#fig3s2
https://elifesciences.org/articles/35677#fig4
https://elifesciences.org/articles/35677#fig5
https://elifesciences.org/articles/35677#fig6
https://elifesciences.org/articles/35677/figures#transrepform
https://elifesciences.org/articles/35677#SA1
https://elifesciences.org/articles/35677#SA2
https://elifesciences.org/articles/35677#respfig1
https://elifesciences.org/articles/35677#respfig2
ae974a485f413a2113503eed53cd6c53
10.7554/eLife.35677
Scopus Count
Collections
Except where otherwise noted, this item's license is described as © 2018, Wang et al. This article is distributed under the terms of the Creative Commons Attribution License.
Related articles
- Sam domain-based stapled peptides: Structural analysis and interaction studies with the Sam domains from the EphA2 receptor and the lipid phosphatase Ship2.
- Authors: Mercurio FA, Pirone L, Di Natale C, Marasco D, Pedone EM, Leone M
- Issue date: 2018 Oct
- The Sam-Sam interaction between Ship2 and the EphA2 receptor: design and analysis of peptide inhibitors.
- Authors: Mercurio FA, Di Natale C, Pirone L, Iannitti R, Marasco D, Pedone EM, Palumbo R, Leone M
- Issue date: 2017 Dec 12
- Structural investigation of a C-terminal EphA2 receptor mutant: Does mutation affect the structure and interaction properties of the Sam domain?
- Authors: Mercurio FA, Costantini S, Di Natale C, Pirone L, Guariniello S, Scognamiglio PL, Marasco D, Pedone EM, Leone M
- Issue date: 2017 Sep
- Exploring a Potential Optimization Route for Peptide Ligands of the Sam Domain from the Lipid Phosphatase Ship2.
- Authors: Vincenzi M, Mercurio FA, La Manna S, Palumbo R, Pirone L, Marasco D, Pedone EM, Leone M
- Issue date: 2024 Oct 2
- Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via phosphatidylinositol 3-Kinase-dependent Rac1 activation.
- Authors: Zhuang G, Hunter S, Hwang Y, Chen J
- Issue date: 2007 Jan 26