Millipore Home

• Home
• Products
• Services
• Learning Center
• Tech Library
• Support
• Company

Product Reference

Matrix metalloproteinase 1 interacts with neuronal integrins and stimulates dephosphorylation of Akt.

Author	Katherine Conant, Coryse St Hillaire, Hideaki Nagase, Rob Visse, Devin Gary, Norman Haughey, Carol Anderson, Jadwiga Turchan, Avindra Nath
Citation Information	The Journal of biological chemistry, 279:8056-62 (2004)
Keywords	Antibodies, Blotting, Western, Brain, Caspases, Cell Survival, Cells, Cultured, Embryo, Mammalian, Enzyme Inhibitors, Humans, Immunohistochemistry, Integrin alpha2beta1, Matrix Metalloproteinase 1, Matrix Metalloproteinase 9, Neurons, Phenylalanine, Phosphorylation, Protein Precursors, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Recombinant Proteins, Signal Transduction, Thiophenes
Related Products	AB1936, AB5320, AB8105, MAB1998Z
Pub Med ID	14679206

Several studies have demonstrated that matrix metalloproteinases (MMPs) are cytotoxic. The responsible mechanisms, however, are not well understood. MMPs may promote cytotoxicity through their ability to disrupt or degrade matrix proteins that support cell survival, and MMPs may also cleave substrates to generate molecules that stimulate cell death. In addition, MMPs may themselves act on cell surface receptors that affect cell survival. Among such receptors is the alpha(2)beta(1) integrin, a complex that has previously been linked to leukocyte death. In the present study we show that human neurons express alpha(2)beta(1) and that pro-MMP-1 interacts with this integrin complex. We also show that stimulation of neuronal cultures with MMP-1 is associated with a rapid reduction in the phosphorylation of Akt, a kinase that can influence caspase activity and cell survival. Moreover, MMP-1-associated dephosphorylation of Akt is inhibited by a blocking antibody to the alpha(2) integrin, but not by batimastat, an inhibitor of MMP-1 enzymatic activity. Such dephosphorylation is also stimulated by a catalytic mutant of pro-MMP-1. Additional studies show that MMP-1 causes neuronal death, which is significantly diminished by both a general caspase inhibitor and anti-alpha(2) but not by batimastat. Together, these results suggest that MMP-1 can stimulate dephosphorylation of Akt and neuronal death through a non-proteolytic mechanism that involves changes in integrin signaling.