Fibronectin type III repeats mediate RGD-independent adhesion and signaling through activated beta1 integrins.
Many cell-surface and extracellular matrix proteins contain multiple modular domains known as fibronectin type III (FNIII) repeats. Cells adhere to the extracellular matrix proteins fibronectin and tenascin in part by the interaction of certain integrins with the Arg-Gly-Asp (RGD) sequence, displayed on specific FNIII repeats. We have found that, after experimental activation of beta1 integrins, a number of cell types adhere and spread on FNIII repeats lacking RGD, derived from extracellular matrix proteins and cytokine receptors. Interaction between individual FNIII domains and beta1 integrins mediates focal adhesion kinase phosphorylation and subsequent stress fiber and focal contact formation. These data suggest that many FNIII-containing proteins may bind and signal through activated beta1 integrins, dramatically expanding the potential for integrin-dependent intercellular and cell-matrix communication.
Chi-Rosso
G
G
Biogen, Inc., Cambridge, Massachusetts 02142, USA.
Gotwals
P J
PJ
Yang
J
J
Ling
L
L
Jiang
K
K
Chao
B
B
Baker
D P
DP
Burkly
L C
LC
Fawell
S E
SE
Koteliansky
V E
VE
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019012:Integrin beta1 / Q000502:physiology*; D008345:Manganese / Q000378:metabolism; D009842:Oligopeptides / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D018121:Receptors, Cytokine / Q000737:chemistry; D015398:Signal Transduction / Q000502:physiology*
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019012:Integrin beta1; D009842:Oligopeptides; D018121:Receptors, Cytokine; D008345:Manganese; C047981:arginyl-glycyl-aspartic acid; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D002118:Calcium