Soluble collagen VI induces tyrosine phosphorylation of paxillin and focaladhesion kinase and activates the MAP kinase Erk2 in fibroblasts

Signals from the extracellular matrix can modulate cellular differentiation and gene expression. We have shown previously that in contrast to other ex tracellular matrix molecules pepsin-solubilized collagen VI (CVI) can stimu late DNA synthesis of various mesenchymal cell types, apparently independen t of integrin-mediated signal transduction. In order to further elucidate c ollagen VI-induced signaling events, we exposed mouse 3T3 fibroblasts and h uman HT1080 fibrosarcoma cells to soluble CVI. CVI induced tyrosine phospho rylation of proteins that associate with focal adhesions, such as paxillin, focal adhesion kinase (FAK), and p130CAS. Furthermore, it activated the mi togen-activated protein kinase, erk2. Kinetic analysis showed that these ph osphorylations were transient, reaching a maximum after 5 min for transform ed HT1080 cells and 30 min for 3T3 fibroblasts. These effects were partly i nhibited by a beta(1)-integrin function blocking antibody and by single cha ins of CVI. Our results indicate that soluble fragments of native collagen VI, a ubiquitous component of the interstitial extracellular matrix, can me diate stimulation of DNA synthesis via tyrosine phosphorylation of paxillin , FAK, p130CAS, and erk2 in the absence of classical growth factors. Thus, CVI may serve as a matrix-derived sensor that allows for rapid reconstituti on of a tissue defect by activating nearby mesenchymal cells. (C) 1999 Acad emic Press.