Matrix metalloproteinase-1 activates a pertussis toxin-sensitive signaling pathway that stimulates the release of matrix metalloproteinase-9

Katherine Conant, Norman Haughey, Avindra Nath, Coryse St. Hillaire, Devin S. Gary, Carlos A Pardo-Villamizar, Larry M. Wahl, Masako Bilak, Elizabeth Milward, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

The matrix metalloproteinases (MMPs) are a family of structurally related metalloendopeptidases so named due to their propensity to target extracellular matrix (ECM) proteins. Accumulating evidence, however, suggests that these proteases cleave numerous non-ECM substrates including enzymes and cell surface receptors. MMPs may also bind to cell surface receptors, though such binding has typically been thought to mediate internalization and degradation of the bound protease. More recently, it has been shown that MMP-1 coimmunoprecipitates with the α2β1 integrin, a receptor for collagen. This association may serve to localize the enzymatic activity of MMP-1 so that collagen is cleaved and cell migration is facilitated. In other studies, however, it has been shown that integrin engagement may be linked to the activation of signaling cascades including those mediated by Giα containing heterotrimers. As an example, α2β1 can form a complex with CD47 that may associate with Giα. In the present study we have therefore investigated the possibility that MMP-1 may affect intracellular changes that are linked to the activation of a Gi protein-coupled receptor. We show that treatment of neural cells with MMP-1 is followed by a rapid reduction in cytosolic levels of cAMP. Moreover, MMP-1 potentiates proteinase activated receptor-1 (PAR-1) agonist-linked increases in intracellular calcium, an effect which is often observed when an agonist of a Gi protein-coupled receptor is administered in association with an agonist of a Gq coupled receptor. In addition, MMP-1 stimulates pertussis toxin sensitive release of MMP-9 both from cultured neural cells and monocyte/macrophages. Together, these results suggest that MMP-1 signals through a pertussis toxin-sensitive G protein-coupled receptor.

Original languageEnglish (US)
Pages (from-to)885-893
Number of pages9
JournalJournal of Neurochemistry
Volume82
Issue number4
DOIs
StatePublished - Aug 2002

Fingerprint

Matrix Metalloproteinase 1
Pertussis Toxin
Matrix Metalloproteinase 9
Cell Surface Receptors
Matrix Metalloproteinases
Integrins
Peptide Hydrolases
Metalloendopeptidases
Chemical activation
Association reactions
Collagen Receptors
PAR-1 Receptor
Macrophages
Extracellular Matrix Proteins
G-Protein-Coupled Receptors
Cell Movement
Monocytes
Cultured Cells
Proteins
Collagen

Keywords

  • CD47
  • G protein-coupled receptor
  • Integrins
  • MMP-1
  • MMP-9

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Matrix metalloproteinase-1 activates a pertussis toxin-sensitive signaling pathway that stimulates the release of matrix metalloproteinase-9. / Conant, Katherine; Haughey, Norman; Nath, Avindra; St. Hillaire, Coryse; Gary, Devin S.; Pardo-Villamizar, Carlos A; Wahl, Larry M.; Bilak, Masako; Milward, Elizabeth; Mattson, Mark P.

In: Journal of Neurochemistry, Vol. 82, No. 4, 08.2002, p. 885-893.

Research output: Contribution to journalArticle

Conant, Katherine ; Haughey, Norman ; Nath, Avindra ; St. Hillaire, Coryse ; Gary, Devin S. ; Pardo-Villamizar, Carlos A ; Wahl, Larry M. ; Bilak, Masako ; Milward, Elizabeth ; Mattson, Mark P. / Matrix metalloproteinase-1 activates a pertussis toxin-sensitive signaling pathway that stimulates the release of matrix metalloproteinase-9. In: Journal of Neurochemistry. 2002 ; Vol. 82, No. 4. pp. 885-893.
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AU - Gary, Devin S.

AU - Pardo-Villamizar, Carlos A

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AU - Mattson, Mark P.

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