The relative roles of collagen adhesive receptor DDR2 activation and matrix stiffness on the downregulation of focal adhesion kinase in vascular smooth muscle cells.
Cells within tissues derive mechanical anchorage and specific molecular signals from the insoluble extracellular matrix (ECM) that surrounds them. Understanding the role of different cues that extracellular matrices provide cells is critical for controlling and predicting cell response to scaffolding materials. Using an engineered extracellular matrix of Type I collagen we examined how the stiffness, supramolecular structure, and glycosylation of collagen matrices influence the protein levels of cellular FAK and the activation of myosin II. Our results show that (1) cellular FAK is downregulated on collagen fibrils, but not on a non-fibrillar monolayer of collagen, (2) the downregulation of FAK is independent of the stiffness of the collagen fibrils, and (3) FAK levels are correlated with levels of tyrosine phosphorylation of the collagen adhesion receptor DDR2. Further, siRNA depletion of DDR2 blocks FAK downregulation. Our results suggest that the collagen receptor DDR2 is involved in the regulation of FAK levels in vSMC adhered to Type I collagen matrices, and that regulation of FAK levels in these cells appears to be independent of matrix stiffness.
Bhadriraju
Kiran
K
SAIC, Mail stop 8313, 100 Bureau Drive, Gaithersburg, MD-20899, USA. kiran.bhadriraju@nist.gov
Chung
Koo-Hyun
KH
Spurlin
Tighe A
TA
Haynes
Ross J
RJ
Elliott
John T
JT
Plant
Anne L
AL
D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D038981:Receptors, Collagen / Q000235:genetics / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*
D024042:Collagen Type I; D038981:Receptors, Collagen; D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases