An alternative processing of integrin αv subunit in tumor cells by membrane type-1 matrix metalloproteinase

Boris I. Ratnikov, Dmitri Rozanov, Tanya I. Postnova, Peter G. Baciu, Heying Zhang, Richard G. Discipio, Galina G. Chestukhina, Jeffrey W. Smith, Elena I. Deryugina, Alex Y. Strongin

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Membrane type-1 matrix metalloproteinase (MT1-MMP) and αvβ3 integrin are both essential to cell invasion. Maturation of integrin pro-αv chain (pro-αv) involves its cleavage by proprotein convertases (PC) to form the disulfide-bonded 125-kDa heavy and 25-kDa light α chains. Our report presents evidence of an alternative pathway of pro-αv processing involving MT1-MMP. In breast carcinoma MCF7 cells deficient in MT1-MMP, pro-αv is processed by a conventional furin-like PC, and the mature αv integrin subunit is represented by the 125-kDa heavy chain and the 25-kDa light chain commencing from the N-terminal Asp891. In contrast, in cells co-expressing αvβ3 and MT1-MMP, MT1-MMP functions as an integrin convertase. MT1-MMP specifically cleaves pro-αv, generating a 115-kDa heavy chain with the truncated C terminus and a 25-kDa light chain commencing from the N-terminal Leu892. PC-cleavable α3 and α5 but not the PC-resistant α2 integrin subunit are also susceptible to MT1-MMP cleavage. These novel mechanisms involved in the processing of integrin α subunits underscore the significance and complexity of interactions between MT1-MMP and adhesion receptors and suggest that regulation of integrin functionality may be an important role of MT1-MMP in migrating tumor cells.

Original languageEnglish (US)
Pages (from-to)7377-7385
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number9
DOIs
StatePublished - Mar 1 2002
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 14
Integrins
Tumors
Cells
Cell Membrane
Proprotein Convertases
Processing
Neoplasms
Light
Proprotein Convertase 2
Melatonin MT1 Receptor
Furin
MCF-7 Cells
Disulfides
Breast Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ratnikov, B. I., Rozanov, D., Postnova, T. I., Baciu, P. G., Zhang, H., Discipio, R. G., ... Strongin, A. Y. (2002). An alternative processing of integrin αv subunit in tumor cells by membrane type-1 matrix metalloproteinase. Journal of Biological Chemistry, 277(9), 7377-7385. https://doi.org/10.1074/jbc.M109580200

An alternative processing of integrin αv subunit in tumor cells by membrane type-1 matrix metalloproteinase. / Ratnikov, Boris I.; Rozanov, Dmitri; Postnova, Tanya I.; Baciu, Peter G.; Zhang, Heying; Discipio, Richard G.; Chestukhina, Galina G.; Smith, Jeffrey W.; Deryugina, Elena I.; Strongin, Alex Y.

In: Journal of Biological Chemistry, Vol. 277, No. 9, 01.03.2002, p. 7377-7385.

Research output: Contribution to journalArticle

Ratnikov, BI, Rozanov, D, Postnova, TI, Baciu, PG, Zhang, H, Discipio, RG, Chestukhina, GG, Smith, JW, Deryugina, EI & Strongin, AY 2002, 'An alternative processing of integrin αv subunit in tumor cells by membrane type-1 matrix metalloproteinase', Journal of Biological Chemistry, vol. 277, no. 9, pp. 7377-7385. https://doi.org/10.1074/jbc.M109580200
Ratnikov, Boris I. ; Rozanov, Dmitri ; Postnova, Tanya I. ; Baciu, Peter G. ; Zhang, Heying ; Discipio, Richard G. ; Chestukhina, Galina G. ; Smith, Jeffrey W. ; Deryugina, Elena I. ; Strongin, Alex Y. / An alternative processing of integrin αv subunit in tumor cells by membrane type-1 matrix metalloproteinase. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 9. pp. 7377-7385.
@article{12bbaf6561374558855970eabb81cb7f,
title = "An alternative processing of integrin αv subunit in tumor cells by membrane type-1 matrix metalloproteinase",
abstract = "Membrane type-1 matrix metalloproteinase (MT1-MMP) and αvβ3 integrin are both essential to cell invasion. Maturation of integrin pro-αv chain (pro-αv) involves its cleavage by proprotein convertases (PC) to form the disulfide-bonded 125-kDa heavy and 25-kDa light α chains. Our report presents evidence of an alternative pathway of pro-αv processing involving MT1-MMP. In breast carcinoma MCF7 cells deficient in MT1-MMP, pro-αv is processed by a conventional furin-like PC, and the mature αv integrin subunit is represented by the 125-kDa heavy chain and the 25-kDa light chain commencing from the N-terminal Asp891. In contrast, in cells co-expressing αvβ3 and MT1-MMP, MT1-MMP functions as an integrin convertase. MT1-MMP specifically cleaves pro-αv, generating a 115-kDa heavy chain with the truncated C terminus and a 25-kDa light chain commencing from the N-terminal Leu892. PC-cleavable α3 and α5 but not the PC-resistant α2 integrin subunit are also susceptible to MT1-MMP cleavage. These novel mechanisms involved in the processing of integrin α subunits underscore the significance and complexity of interactions between MT1-MMP and adhesion receptors and suggest that regulation of integrin functionality may be an important role of MT1-MMP in migrating tumor cells.",
author = "Ratnikov, {Boris I.} and Dmitri Rozanov and Postnova, {Tanya I.} and Baciu, {Peter G.} and Heying Zhang and Discipio, {Richard G.} and Chestukhina, {Galina G.} and Smith, {Jeffrey W.} and Deryugina, {Elena I.} and Strongin, {Alex Y.}",
year = "2002",
month = "3",
day = "1",
doi = "10.1074/jbc.M109580200",
language = "English (US)",
volume = "277",
pages = "7377--7385",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "9",

}

TY - JOUR

T1 - An alternative processing of integrin αv subunit in tumor cells by membrane type-1 matrix metalloproteinase

AU - Ratnikov, Boris I.

AU - Rozanov, Dmitri

AU - Postnova, Tanya I.

AU - Baciu, Peter G.

AU - Zhang, Heying

AU - Discipio, Richard G.

AU - Chestukhina, Galina G.

AU - Smith, Jeffrey W.

AU - Deryugina, Elena I.

AU - Strongin, Alex Y.

PY - 2002/3/1

Y1 - 2002/3/1

N2 - Membrane type-1 matrix metalloproteinase (MT1-MMP) and αvβ3 integrin are both essential to cell invasion. Maturation of integrin pro-αv chain (pro-αv) involves its cleavage by proprotein convertases (PC) to form the disulfide-bonded 125-kDa heavy and 25-kDa light α chains. Our report presents evidence of an alternative pathway of pro-αv processing involving MT1-MMP. In breast carcinoma MCF7 cells deficient in MT1-MMP, pro-αv is processed by a conventional furin-like PC, and the mature αv integrin subunit is represented by the 125-kDa heavy chain and the 25-kDa light chain commencing from the N-terminal Asp891. In contrast, in cells co-expressing αvβ3 and MT1-MMP, MT1-MMP functions as an integrin convertase. MT1-MMP specifically cleaves pro-αv, generating a 115-kDa heavy chain with the truncated C terminus and a 25-kDa light chain commencing from the N-terminal Leu892. PC-cleavable α3 and α5 but not the PC-resistant α2 integrin subunit are also susceptible to MT1-MMP cleavage. These novel mechanisms involved in the processing of integrin α subunits underscore the significance and complexity of interactions between MT1-MMP and adhesion receptors and suggest that regulation of integrin functionality may be an important role of MT1-MMP in migrating tumor cells.

AB - Membrane type-1 matrix metalloproteinase (MT1-MMP) and αvβ3 integrin are both essential to cell invasion. Maturation of integrin pro-αv chain (pro-αv) involves its cleavage by proprotein convertases (PC) to form the disulfide-bonded 125-kDa heavy and 25-kDa light α chains. Our report presents evidence of an alternative pathway of pro-αv processing involving MT1-MMP. In breast carcinoma MCF7 cells deficient in MT1-MMP, pro-αv is processed by a conventional furin-like PC, and the mature αv integrin subunit is represented by the 125-kDa heavy chain and the 25-kDa light chain commencing from the N-terminal Asp891. In contrast, in cells co-expressing αvβ3 and MT1-MMP, MT1-MMP functions as an integrin convertase. MT1-MMP specifically cleaves pro-αv, generating a 115-kDa heavy chain with the truncated C terminus and a 25-kDa light chain commencing from the N-terminal Leu892. PC-cleavable α3 and α5 but not the PC-resistant α2 integrin subunit are also susceptible to MT1-MMP cleavage. These novel mechanisms involved in the processing of integrin α subunits underscore the significance and complexity of interactions between MT1-MMP and adhesion receptors and suggest that regulation of integrin functionality may be an important role of MT1-MMP in migrating tumor cells.

UR - http://www.scopus.com/inward/record.url?scp=18544367658&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18544367658&partnerID=8YFLogxK

U2 - 10.1074/jbc.M109580200

DO - 10.1074/jbc.M109580200

M3 - Article

C2 - 11741954

AN - SCOPUS:18544367658

VL - 277

SP - 7377

EP - 7385

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 9

ER -