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J Biol Chem, Vol. 273, Issue 40, 25533-25536, October 2, 1998
From the Department of Molecular Biology, Princeton University,
Princeton, New Jersey 08544
Developmental patterning and differentiation,
maintenance of parenchymal cell function, and the size, shape, and
invasiveness of tumors are all orchestrated by cell interactions with
the extracellular matrix. Here we show that the fibrillar structure of
fibronectin (FN) matrix encodes essential regulatory cues and controls
cell proliferation and signaling through changes in matrix
architecture. A matrix assembled from native FN stimulated cell growth.
In contrast, a mutant FN (FN
III1-7) that contains
all known cell binding motifs but forms a structurally distinct matrix
inhibited progression from G0/G1 into S phase.
Furthermore, FNIII1-7 suppressed the stimulatory
capacity of native FN and induced different levels of tyrosine
phosphorylation of pp125FAK. The differential effects on
cell growth were ablated by blocking formation of matrix fibrils. Thus,
modification of matrix architecture provides a novel approach to
control cell proliferation.
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