| Abstract |
The N-glycosylation of integrin α5β1 is involved in multiple cell biological functions. Our group previously reported that the N-glycosylation of the Calf-1,2 domain on α5 subunit (S3-5,10-14) was important for its inhibitory effect on EGFR signaling through regulating α5-EGFR complex formation. In this follow-up study, we provide evidence that the N-glycosylation on integrin β1 subunit suppress cell growth by promoting its association with EGFR under fibronectin (FN)-coated conditions. Expression of wild-type (WT) β1, but not the N-glycosylation mutant S4-6 β1, which contains fewer N-glycans, inhibited EGFR signaling and cell proliferation after cell adhesion to FN. Furthermore, consistent restoration of the N-glycans on sites 1-3 of β1 reinstated the inhibitory effects. Mechanistically, the N-glycosylation mutant of β1 (S4-6+1-3) inhibited the EGFR response upon EGF stimulation via facilitating the α5β1-EGFR complex formation. Moreover, we identified the N-glycosylation of sites 10-14 on α5 and 1-3 on β1 were most important for EGFR signaling. Taken together, these data indicate that α5S3-5+10-14β1S4-6+1-3 mutant represents the minimal N-glycosylation required for its regulation on EGFR signaling and cell proliferation, providing a plausible mechanism for the crosstalk between with α5β1 and EGFR.
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