Direct integrin αvβ6-ERK binding: implications for tumour growth
| Autor: | Michael Agrez, Nuzhat Ahmed, Mark S. Baker, Jun Niu, Sarah Andrews, Ian Macreadie, Rodney J. Scott, Douglas J. Dorahy, Cliff Meldrum, Xinhua Gu |
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| Rok vydání: | 2002 |
| Předmět: |
MAPK/ERK pathway
Integrins Cancer Research medicine.medical_specialty Transcription Genetic Molecular Sequence Data Integrin Enzyme-Linked Immunosorbent Assay Mitogen-activated protein kinase kinase CD49c DNA Antisense Cytosol Antigens Neoplasm Neoplasms Internal medicine Tumor Cells Cultured Genetics medicine Humans Amino Acid Sequence RNA Messenger Growth Substances Molecular Biology Sequence Deletion Binding Sites biology MAP kinase kinase kinase Kinase Flow Cytometry Peptide Fragments Protein Structure Tertiary Cell biology Protein Subunits Endocrinology Integrin alpha M biology.protein Integrin beta 6 Streptavidin Mitogen-Activated Protein Kinases Cell Division Protein Binding |
| Zdroj: | Oncogene. 21:1370-1380 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Blockade of the mitogen-activated protein (MAP) kinase pathway suppresses growth of colon cancer in vivo. Here we demonstrate a direct link between the extracellular signal-regulated kinase ERK2 and the growth-promoting cell adhesion molecule, integrin alphavbeta6, in colon cancer cells. Down-regulation of beta6 integrin subunit expression inhibits tumour growth in vivo and MAP kinase activity in response to serum stimulation. In alphavbeta6-expressing cells ERK2 is bound only to the beta6 subunit. The increase in cytosolic MAP kinase activity upon epidermal growth factor stimulation is all accounted for by beta6-bound ERK. Deletion of the ERK2 binding site on the beta6 cytoplasmic domain inhibits tumour growth and leads to an association between ERK and the beta5 subunit. The physical interaction between integrin alphavbeta6 and ERK2 defines a novel paradigm of integrin-mediated signalling and provides a therapeutic target for cancer treatment. |
| Databáze: | OpenAIRE |
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