Involvement of Pp60c-src with Two Major Signaling Pathways in Human Breast Cancer

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1994 Jan 4

PMID 7506422

Citations 64

Authors

D K Luttrell

A Lee

T J Lansing

R M Crosby

K D Jung

D Willard

M Luther

M Rodriguez

J Berman

T M Gilmer

Affiliations

Soon will be listed here.

Abstract

The phosphotyrosine residues of receptor tyrosine kinases serve as unique binding sites for proteins involved in intracellular signaling, which contain SRC homology 2 (SH2) domains. Since overexpression or activation of the pp60c-src kinase has been reported in a number of human tumors, including primary human breast carcinomas, we examined the interactions of the SH2 and SH3 domains of human SRC with target proteins in human carcinoma cell lines. Glutathione S-transferase fusion proteins containing either the SH2, SH3, or the entire SH3/SH2 region of human SRC were used to affinity purify tyrosine-phosphorylated proteins from human breast carcinoma cell lines. We show here that in human breast carcinoma cell lines, the SRC SH2 domain binds to activated epidermal growth factor receptor (EGFR) and p185HER2/neu. SRC SH2 binding to EGFR was also observed in a nontumorigenic cell line after hormone stimulation. Endogenous pp60c-src was found to tightly associate with tyrosine-phosphorylated EGFR. Association of the SRC SH2 with the EGFR was blocked by tyrosyl phosphopeptides containing the sequences surrounding tyrosine-530, the regulatory site in the SRC C terminus, or sequences surrounding the major sites of autophosphorylation in the EGFR. These results raise the possibility that association of pp60c-src with these receptor tyrosine kinases is an integral part of the signaling events mediated by these receptors and may contribute to malignant transformation.

Citing Articles

Increased c‑SRC expression is involved in acquired resistance to lenvatinib in hepatocellular carcinoma.

Takahashi M, Araki T, Yashima H, Nagamine A, Nagano D, Yamamoto K Oncol Lett. 2023; 26(6):529.

PMID: 38020292 PMC: 10654551. DOI: 10.3892/ol.2023.14116.

New Structural Perspectives in G Protein-Coupled Receptor-Mediated Src Family Kinase Activation.

Berndt S, Liebscher I Int J Mol Sci. 2021; 22(12).

PMID: 34204297 PMC: 8233884. DOI: 10.3390/ijms22126489.

Standard of Care and Promising New Agents for the Treatment of Mesenchymal Triple-Negative Breast Cancer.

Mezi S, Botticelli A, Pomati G, Cerbelli B, Scagnoli S, Amirhassankhani S Cancers (Basel). 2021; 13(5).

PMID: 33802438 PMC: 7959307. DOI: 10.3390/cancers13051080.

Cortactin in Epithelial-Mesenchymal Transition.

Ji R, Zhu X, Wang Z, Huang L Front Cell Dev Biol. 2020; 8:585619.

PMID: 33195233 PMC: 7606982. DOI: 10.3389/fcell.2020.585619.

c-Src and EGFR Inhibition in Molecular Cancer Therapy: What Else Can We Improve?.

Belli S, Esposito D, Servetto A, Pesapane A, Formisano L, Bianco R Cancers (Basel). 2020; 12(6).

PMID: 32517369 PMC: 7352780. DOI: 10.3390/cancers12061489.

References

Slamon D, Godolphin W, Jones L, Holt J, Wong S, Keith D . Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989; 244(4905):707-12. DOI: 10.1126/science.2470152. View

Wilson L, Luttrell D, Parsons J, Parsons S . pp60c-src tyrosine kinase, myristylation, and modulatory domains are required for enhanced mitogenic responsiveness to epidermal growth factor seen in cells overexpressing c-src. Mol Cell Biol. 1989; 9(4):1536-44. PMC: 362570. DOI: 10.1128/mcb.9.4.1536-1544.1989. View

Luttrell D, Luttrell L, Parsons S . Augmented mitogenic responsiveness to epidermal growth factor in murine fibroblasts that overexpress pp60c-src. Mol Cell Biol. 1988; 8(1):497-501. PMC: 363160. DOI: 10.1128/mcb.8.1.497-501.1988. View

Tanaka A, Gibbs C, Arthur R, Anderson S, Kung H, Fujita D . DNA sequence encoding the amino-terminal region of the human c-src protein: implications of sequence divergence among src-type kinase oncogenes. Mol Cell Biol. 1987; 7(5):1978-83. PMC: 365305. DOI: 10.1128/mcb.7.5.1978-1983.1987. View

Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W . Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785):177-82. DOI: 10.1126/science.3798106. View

Singletary S, Baker F, Spitzer G, Tucker S, Tomasovic B, Brock W . Biological effect of epidermal growth factor on the in vitro growth of human tumors. Cancer Res. 1987; 47(2):403-6. View

Ralston R, Bishop J . The product of the protooncogene c-src is modified during the cellular response to platelet-derived growth factor. Proc Natl Acad Sci U S A. 1985; 82(23):7845-9. PMC: 390866. DOI: 10.1073/pnas.82.23.7845. View

Semba K, Kamata N, Toyoshima K, Yamamoto T . A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc Natl Acad Sci U S A. 1985; 82(19):6497-501. PMC: 390744. DOI: 10.1073/pnas.82.19.6497. View

Anderson S, Gibbs C, Tanaka A, Kung H, Fujita D . Human cellular src gene: nucleotide sequence and derived amino acid sequence of the region coding for the carboxy-terminal two-thirds of pp60c-src. Mol Cell Biol. 1985; 5(5):1122-9. PMC: 366830. DOI: 10.1128/mcb.5.5.1122-1129.1985. View

10.

Filmus J, Pollak M, CAILLEAU R, Buick R . MDA-468, a human breast cancer cell line with a high number of epidermal growth factor (EGF) receptors, has an amplified EGF receptor gene and is growth inhibited by EGF. Biochem Biophys Res Commun. 1985; 128(2):898-905. DOI: 10.1016/0006-291x(85)90131-7. View

11.

Schechter A, Stern D, Vaidyanathan L, Decker S, Drebin J, Greene M . The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984; 312(5994):513-6. DOI: 10.1038/312513a0. View

12.

Songyang Z, Shoelson S, Chaudhuri M, Gish G, Pawson T, Haser W . SH2 domains recognize specific phosphopeptide sequences. Cell. 1993; 72(5):767-78. DOI: 10.1016/0092-8674(93)90404-e. View

13.

Sierke S, Longo G, Koland J . Structural basis of interactions between epidermal growth factor receptor and SH2 domain proteins. Biochem Biophys Res Commun. 1993; 191(1):45-54. DOI: 10.1006/bbrc.1993.1182. View

14.

Luttrell D, Hausdorff W, Moyers J, Gilmer T, Parsons S, Caron M . Overexpression of pp60c-src is associated with altered regulation of adenylyl cyclase. Cell Signal. 1992; 4(5):531-41. DOI: 10.1016/0898-6568(92)90022-z. View

15.

Twamley G, Kypta R, Hall B, Courtneidge S . Association of Fyn with the activated platelet-derived growth factor receptor: requirements for binding and phosphorylation. Oncogene. 1992; 7(10):1893-901. View

16.

Andrews D, Kitchin J, Seale P . Solid-phase synthesis of a range of O-phosphorylated peptides by post-assembly phosphitylation and oxidation. Int J Pept Protein Res. 1991; 38(5):469-75. DOI: 10.1111/j.1399-3011.1991.tb01528.x. View

17.

Rijksen G, van Beurden E, Hennipman A, Michels A, Staal G . Characterization of protein tyrosine kinases from human breast cancer: involvement of the c-src oncogene product. Cancer Res. 1992; 52(17):4773-8. View

18.

Liu X, Brodeur S, Gish G, Songyang Z, Cantley L, Laudano A . Regulation of c-Src tyrosine kinase activity by the Src SH2 domain. Oncogene. 1993; 8(5):1119-26. View

19.

Roussel R, Brodeur S, Shalloway D, Laudano A . Selective binding of activated pp60c-src by an immobilized synthetic phosphopeptide modeled on the carboxyl terminus of pp60c-src. Proc Natl Acad Sci U S A. 1991; 88(23):10696-700. PMC: 52997. DOI: 10.1073/pnas.88.23.10696. View

20.

Koch C, Anderson D, Moran M, Ellis C, Pawson T . SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991; 252(5006):668-74. DOI: 10.1126/science.1708916. View