Phosphotyrosine Interactome of the ErbB-receptor Kinase Family

Overview

Journal Mol Syst Biol

Specialty Molecular Biology

Date 2006 May 27

PMID 16729043

Citations 249

Authors

Waltraud X Schulze

Lei Deng

Matthias Mann

Affiliations

Soon will be listed here.

Abstract

Interactions between short modified peptide motifs and modular protein domains are central events in cell signal-transduction. We determined interaction partners to all cytosolic tyrosine residues of the four members of the ErbB-receptor family in an unbiased fashion by quantitative proteomics using pull-down experiments with pairs of phosphorylated and nonphosphorylated synthetic peptides. Each receptor had characteristic preferences for interacting proteins and most interaction partners had multiple binding sites on each receptor. EGFR and ErbB4 had several docking sites for Grb2, while ErbB3 was characterized by six binding sites for PI3K. We identified STAT5 as a direct binding partner to EGFR and ErbB4 and discovered new recognition motifs for Shc and STAT5. The overall pattern of interaction partners of EGFR and ErbB4 suggests similar roles during signaling through their respective ligands. Phosphorylation kinetics of several tyrosine resides was measured by mass spectrometry and correlated with interaction partner preference. Our results demonstrate that system-wide mapping of peptide-protein interactions sites is possible, and suggest shared and unique roles of ErbB-receptor family members in downstream signaling.

Citing Articles

Cell Adhesion Molecules as Modulators of the Epidermal Growth Factor Receptor.

Kozlova I, Sytnyk V Cells. 2024; 13(22).

PMID: 39594667 PMC: 11592701. DOI: 10.3390/cells13221919.

Targeting the Epidermal Growth Factor Receptor Pathway in Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase II Study.

Yam C, Patel M, Hill H, Sun R, Bassett Jr R, Kong E Cancer Res Commun. 2024; 4(10):2823-2834.

PMID: 39356138 PMC: 11520071. DOI: 10.1158/2767-9764.CRC-24-0255.

Dissecting phospho-motif-dependent Shc1 interactome using long synthetic protein fragments.

Chen P, Chen X, Song X, He A, Zheng Y, Li X Chem Sci. 2024; .

PMID: 39184293 PMC: 11342145. DOI: 10.1039/d4sc02350a.

Enzyme Is the Name-Adapter Is the Game.

Huber M, Brummer T Cells. 2024; 13(15.

PMID: 39120280 PMC: 11311582. DOI: 10.3390/cells13151249.

Transcriptome analysis of cynomolgus macaques throughout their lifespan reveals age-related immune patterns.

Cho H, Choe S, Lee J, Park H, Ko M, Lee Y NPJ Aging. 2024; 10(1):30.

PMID: 38902280 PMC: 11189941. DOI: 10.1038/s41514-024-00158-0.

References

Pawson T . Specificity in signal transduction: from phosphotyrosine-SH2 domain interactions to complex cellular systems. Cell. 2004; 116(2):191-203. DOI: 10.1016/s0092-8674(03)01077-8. View

Andersen J, Wilkinson C, Mayor T, Mortensen P, Nigg E, Mann M . Proteomic characterization of the human centrosome by protein correlation profiling. Nature. 2003; 426(6966):570-4. DOI: 10.1038/nature02166. View

Schulze W, Mann M . A novel proteomic screen for peptide-protein interactions. J Biol Chem. 2003; 279(11):10756-64. DOI: 10.1074/jbc.M309909200. View

Landgraf C, Panni S, Montecchi-Palazzi L, Castagnoli L, Schneider-Mergener J, Volkmer-Engert R . Protein interaction networks by proteome peptide scanning. PLoS Biol. 2004; 2(1):E14. PMC: 314469. DOI: 10.1371/journal.pbio.0020014. View

Olsen J, Ong S, Mann M . Trypsin cleaves exclusively C-terminal to arginine and lysine residues. Mol Cell Proteomics. 2004; 3(6):608-14. DOI: 10.1074/mcp.T400003-MCP200. View

Blagoev B, Ong S, Kratchmarova I, Mann M . Temporal analysis of phosphotyrosine-dependent signaling networks by quantitative proteomics. Nat Biotechnol. 2004; 22(9):1139-45. DOI: 10.1038/nbt1005. View

Goehler H, Lalowski M, Stelzl U, Waelter S, Stroedicke M, Worm U . A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease. Mol Cell. 2004; 15(6):853-65. DOI: 10.1016/j.molcel.2004.09.016. View

Smith B, Chin D, Maltzman W, Crosby K, Hortobagyi G, Bacus S . The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins. Br J Cancer. 2004; 91(6):1190-4. PMC: 2747699. DOI: 10.1038/sj.bjc.6602090. View

Margolis B, Li N, Koch A, Mohammadi M, Hurwitz D, Zilberstein A . The tyrosine phosphorylated carboxyterminus of the EGF receptor is a binding site for GAP and PLC-gamma. EMBO J. 1990; 9(13):4375-80. PMC: 552227. DOI: 10.1002/j.1460-2075.1990.tb07887.x. View

10.

Rotin D, Margolis B, Mohammadi M, Daly R, Daum G, Li N . SH2 domains prevent tyrosine dephosphorylation of the EGF receptor: identification of Tyr992 as the high-affinity binding site for SH2 domains of phospholipase C gamma. EMBO J. 1992; 11(2):559-67. PMC: 556487. DOI: 10.1002/j.1460-2075.1992.tb05087.x. View

11.

Birge R, Fajardo J, Mayer B, Hanafusa H . Tyrosine-phosphorylated epidermal growth factor receptor and cellular p130 provide high affinity binding substrates to analyze Crk-phosphotyrosine-dependent interactions in vitro. J Biol Chem. 1992; 267(15):10588-95. View

12.

Fedi P, PIERCE J, Di Fiore P, Kraus M . Efficient coupling with phosphatidylinositol 3-kinase, but not phospholipase C gamma or GTPase-activating protein, distinguishes ErbB-3 signaling from that of other ErbB/EGFR family members. Mol Cell Biol. 1994; 14(1):492-500. PMC: 358399. DOI: 10.1128/mcb.14.1.492-500.1994. View

13.

Songyang Z, Shoelson S, McGlade J, Olivier P, Pawson T, Bustelo X . Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav. Mol Cell Biol. 1994; 14(4):2777-85. PMC: 358643. DOI: 10.1128/mcb.14.4.2777-2785.1994. View

14.

Prigent S, Gullick W . Identification of c-erbB-3 binding sites for phosphatidylinositol 3'-kinase and SHC using an EGF receptor/c-erbB-3 chimera. EMBO J. 1994; 13(12):2831-41. PMC: 395164. DOI: 10.1002/j.1460-2075.1994.tb06577.x. View

15.

Gustafson T, He W, Craparo A, Schaub C, ONeill T . Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain. Mol Cell Biol. 1995; 15(5):2500-8. PMC: 230480. DOI: 10.1128/MCB.15.5.2500. View

16.

Schumacher C, Knudsen B, Ohuchi T, Di Fiore P, Glassman R, Hanafusa H . The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R. J Biol Chem. 1995; 270(25):15341-7. DOI: 10.1074/jbc.270.25.15341. View

17.

Stover D, Becker M, Liebetanz J, Lydon N . Src phosphorylation of the epidermal growth factor receptor at novel sites mediates receptor interaction with Src and P85 alpha. J Biol Chem. 1995; 270(26):15591-7. DOI: 10.1074/jbc.270.26.15591. View

18.

Lombardo C, Consler T, Kassel D . In vitro phosphorylation of the epidermal growth factor receptor autophosphorylation domain by c-src: identification of phosphorylation sites and c-src SH2 domain binding sites. Biochemistry. 1995; 34(50):16456-66. DOI: 10.1021/bi00050a029. View

19.

Ward C, Gough K, Rashke M, Wan S, Tribbick G, Wang J . Systematic mapping of potential binding sites for Shc and Grb2 SH2 domains on insulin receptor substrate-1 and the receptors for insulin, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor. J Biol Chem. 1996; 271(10):5603-9. DOI: 10.1074/jbc.271.10.5603. View

20.

Sorkin A, Mazzotti M, Sorkina T, Scotto L, Beguinot L . Epidermal growth factor receptor interaction with clathrin adaptors is mediated by the Tyr974-containing internalization motif. J Biol Chem. 1996; 271(23):13377-84. DOI: 10.1074/jbc.271.23.13377. View