P. Sanchezaparicio et al., ACTIVATION OF THE ALPHA-4-BETA-1 INTEGRIN THROUGH THE BETA-1 SUBUNIT INDUCES RECOGNITION OF THE RGDS SEQUENCE IN FIBRONECTIN, The Journal of cell biology, 126(1), 1994, pp. 271-279
Lymphocyte attachment to fibronectin is mainly mediated by the interac
tion of alpha 5 beta 1 and alpha 4 beta 1 integrins with the RGD and C
S-1/Hep II sites, respectively. We have recently shown that the anti-b
eta 1 mAb TS2/16 can convert the partly active alpha 4 beta 1 present
on certain hemopoietic cells that recognizes CS-1 but not Hep II, to a
high avidity form that binds both ligands. In this report we have stu
died whether mAb TS2/16 also affects alpha 4 beta 1 ligand specificity
. Incubation of the B cell, lines Ramos and Daudi (which lack (alpha 5
beta 1)) with mAb TS2/16 induced specific attachment to an 80-kD frag
ment which lacks CS-1 and Hep II and contains the RGD sequence. mAbs a
nti-alpha 4 and the synthetic peptides CS-1 and IDAPS inhibited adhesi
on to the 80-kD fragment thus implying alpha 4 beta 1 as the receptor
for this fragment. Interestingly, the synthetic peptide GRGDSPC and a
15-kD peptic fibronectin fragment containing the RGD sequence also inh
ibited B cell adhesion to the 80-kD fragment. Because we have previous
ly shown that RGD peptides do not affect the constitutive function of
alpha 4 beta 1, we tested whether TS2/16-activated alpha 4 beta 1 acqu
ired the capacity to recognize RGD. Indeed RGD peptides inhibited TS2/
16-treated B cell adhesion to a 38-kD fragment containing CS-1 and Hep
II but did not affect binding of untreated cells to this fragment. An
anti-fibronectin mAb reactive with an epitope on or near the RGD sequ
ence also efficiently inhibited cell adhesion to the 80-kD fragment, i
ndicating that the RGD sequence is a novel adhesive ligand for activat
ed alpha 4 beta 1. These results emphasize the role of alpha 4 beta 1
as a receptor with different ligand specificities according to the act
ivation state, a fact that may be important for lymphocyte migration,
localization, and function.