The integrin cytoplasmic-tail motif EKQKVDLSTDC is sufficient to promote tumor cell invasion mediated by matrix metalloproteinase (MMP)-2 or MMP-9
The integrin cytoplasmic-tail motif EKQKVDLSTDC is sufficient to promote tumor cell invasion mediated by matrix metalloproteinase (MMP)-2 or MMP-9
Integrins promote cellular invasion through a combination of activities, including adhesion to an extracellular matrix ligand, which result in the generation of intracellular signals that lead to changes in cell behavior. Until now, there have been no data that identify a particular region of the cytoplasmic tail of integrin subunits as being responsible specifically for promoting the invasive activity of tumor cells. In this report, we show that amino acids with the sequence EKQKVDLSTDC, which are the C-terminal residues of the integrin ?6 subunit, promote ?v?6-dependent invasion in a matrix metalloproteinase (MMP)-9-dependent fashion. This same peptide sequence, when expressed at the cytoplasmic end of the ?3 integrin subunit, was able to enhance ?v?3-mediated invasive and enzymatic activity of tumor cells in an MMP-2-dependent fashion. Our results show that these 11 amino acids, when expressed at the C terminus of the ? subunit, are responsible for regulating the activity of invasion-promoting degradative enzymes, whereas the specific MMP involved in this cellular behavior is dependent on the context of the remainder of the ? integrin subunit.
26533-26539
Morgan, Mark R.
8905660d-a029-4da7-b50c-13fbd24b0c7f
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Russell, Alan
3db00588-973e-49d0-8c42-84dcb82bc697
Hart, Ian R.
6a3728fc-5385-4dd4-a5e3-edd5168a0e8d
Marshall, John F
bc569c17-f2b8-4085-a6ff-d4a42da43c27
18 June 2004
Morgan, Mark R.
8905660d-a029-4da7-b50c-13fbd24b0c7f
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Russell, Alan
3db00588-973e-49d0-8c42-84dcb82bc697
Hart, Ian R.
6a3728fc-5385-4dd4-a5e3-edd5168a0e8d
Marshall, John F
bc569c17-f2b8-4085-a6ff-d4a42da43c27
Morgan, Mark R., Thomas, Gareth J., Russell, Alan, Hart, Ian R. and Marshall, John F
(2004)
The integrin cytoplasmic-tail motif EKQKVDLSTDC is sufficient to promote tumor cell invasion mediated by matrix metalloproteinase (MMP)-2 or MMP-9.
The Journal of Biological Chemistry, 279 (25), .
(doi:10.1074/jbc.M401736200).
Abstract
Integrins promote cellular invasion through a combination of activities, including adhesion to an extracellular matrix ligand, which result in the generation of intracellular signals that lead to changes in cell behavior. Until now, there have been no data that identify a particular region of the cytoplasmic tail of integrin subunits as being responsible specifically for promoting the invasive activity of tumor cells. In this report, we show that amino acids with the sequence EKQKVDLSTDC, which are the C-terminal residues of the integrin ?6 subunit, promote ?v?6-dependent invasion in a matrix metalloproteinase (MMP)-9-dependent fashion. This same peptide sequence, when expressed at the cytoplasmic end of the ?3 integrin subunit, was able to enhance ?v?3-mediated invasive and enzymatic activity of tumor cells in an MMP-2-dependent fashion. Our results show that these 11 amino acids, when expressed at the C terminus of the ? subunit, are responsible for regulating the activity of invasion-promoting degradative enzymes, whereas the specific MMP involved in this cellular behavior is dependent on the context of the remainder of the ? integrin subunit.
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Published date: 18 June 2004
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Local EPrints ID: 66690
URI: http://eprints.soton.ac.uk/id/eprint/66690
ISSN: 0021-9258
PURE UUID: 19104f53-5bc9-44fe-9505-41a6f209eefe
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Date deposited: 10 Jul 2009
Last modified: 13 Mar 2024 18:30
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Author:
Mark R. Morgan
Author:
Alan Russell
Author:
Ian R. Hart
Author:
John F Marshall
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