tailieunhanh - Báo cáo khoa học: Epidermal growth factor receptor ligands as new extracellular targets for the metastasis-promoting S100A4 protein

The function of S100A4, a member of the calcium-binding S100 protein family, has been associated with tumor invasion and metastasis. Although an essential pro-metastatic role of extracellular S100A4 in tumor progres-sion has been demonstrated, the identification of the precise underlying mechanisms and protein partners (receptors) has remained elusive. | ễFEBS Journal Epidermal growth factor receptor ligands as new extracellular targets for the metastasis-promoting S100A4 protein lof ri 1 11 nfloI hofot 1 I Ion riIf r l l TỈ I loi 1 Ft on I I Cĩ 11 mo r 1 h r ĩ ct Ĩ a Q I I Rofn 1 Ỷ a ri a Po111 o 1 Joiy Kiinyeinuier neiHik D. ivi0iiei Lien U. ouiiici I diiioiiaii n. Deiy Ậ Iviaiia ruuiocii Darya Kiryushko2 Vladislav Soroka2 Noona Ambartsumian1 Mariam Griyorian1 and Euyene M. Lukanidin1 1 Department of Molecular Cancer Biology Institute of Cancer Biology Danish Cancer Society Copenhagen Denmark 2 Protein Laboratory Institute of Molecular Pathology Panum Institute Copenhagen Denmark Keywords amphiregulin EGFR ligand phage display peptide library protein-protein interaction S100A4 Correspondence J. Klingelhofer Strandboulevarden 49 2100 Copenhagen 0 Denmark Fax 45 35257721 Tel 45 35257761 E-mail jkl@ Present addresses Albert Einstein College of Medicine Department of Biochemistry Bronx NY USA ỊMolecular Pathology Section BRIC Copenhagen Biocenter Denmark These authors contributed equally to this work Received 10 May 2009 revised 20 July 2009 accepted 11 August 2009 doi The function of S100A4 a member of the calcium-binding S100 protein family has been associated with tumor invasion and metastasis. Although an essential pro-metastatic role of extracellular S100A4 in tumor progression has been demonstrated the identification of the precise underlying mechanisms and protein partners receptors has remained elusive. To identify putative targets for extracellular S100A4 we screened a phage display peptide library using S100A4 as bait. We identified three independent peptide motifs with varying affinities for the S100A4 protein. Sequence analyses indicated that the most abundant peptide mimicked the F YCC motif present in the epidermal growth factor domain of ErbB receptor ligands. S100A4 selectively interacted with a number of epidermal growth factor receptor EGFR ligands .