Cellular interactions with the extracellular matrix are coupled to diverse transmembrane signaling pathways

Exp Cell Res. 1992 Dec;203(2):365-73. doi: 10.1016/0014-4827(92)90010-6.

Abstract

Extracellular matrix (ECM) glycoproteins such as laminin, fibronectin, or collagen IV play a major role in cell behavior regulation. The molecular mechanisms taking place at the interface between the ECM and the cell surface are now rather well defined; however, very little is known about intracellular signals induced by these interactions. In order to get insights into the transduction pathways involved in cell-ECM interactions we have investigated the effects of several intracellular kinase inhibitors. Calmodulin-dependent kinase inhibitors, W-7 and sphingosine, have negative effects on cell-matrix interactions. They inhibit adhesion of several cell lines to laminin (IC50 = 4-10 microM), fibronectin and collagen IV (IC50 = 7-25 microM). The effects are immediate, reversible, and also cell specific, certain combinations of cell line-substrate being irresponsive to these inhibitors. In contrast, two inhibitors, H-7 and staurosporine, for which protein kinase C is a common target, increase two- to fourfold the attachment of HT1080, OVCAR-4, and B16F10 cells to laminin but not to fibronectin. Another inhibitor, HA-1004, known to inhibit protein kinase A at low concentrations, has an activating effect only at high concentration (> 200 microM) when it becomes an inhibitor of protein kinase C. These inhibitors are without effect on RuGli and Saos-2 cell adhesion on the three substrates. Altogether these results suggest that calmodulin-dependent kinases and protein kinase C could be separately involved in ECM-induced cellular responses. However, the effects of kinase inhibitors are substrate-specific and cell type-specific, suggesting that the intracellular signals induced by the extracellular matrix vary with the nature of integrin involved in signal transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Alkaloids / pharmacology
  • Animals
  • Calmodulin / pharmacology
  • Cell Adhesion*
  • Collagen / metabolism
  • Extracellular Matrix / physiology*
  • Extracellular Matrix Proteins / metabolism*
  • Fibronectins / metabolism
  • Humans
  • Isoquinolines / pharmacology
  • Laminin / metabolism
  • Piperazines / pharmacology
  • Protein Kinase C / metabolism
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism*
  • Signal Transduction*
  • Staurosporine
  • Sulfonamides*
  • Tumor Cells, Cultured

Substances

  • Alkaloids
  • Calmodulin
  • Extracellular Matrix Proteins
  • Fibronectins
  • Isoquinolines
  • Laminin
  • Piperazines
  • Protein Kinase Inhibitors
  • Sulfonamides
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Collagen
  • N-(2-guanidinoethyl)-5-isoquinolinesulfonamide
  • Protein Kinases
  • Protein Kinase C
  • Staurosporine