Phosphorylation of beta3 integrin controls ligand binding strength.
The cytoplasmic domain of beta(3) integrin contains tyrosines at positions 747 and 759 in domains that have been implicated in regulation of alpha(v)beta(3) function and that serve as potential substrates for Src family kinases. The phosphorylation level of beta(3) integrin was modulated using a temperature-sensitive v-Src kinase. Increased beta(3) phosphorylation abolished alpha(v)beta(3)- but not alpha(5)beta(1)-mediated adhesion to fibronectin. alpha(v)beta(3)-Mediated cell adhesion was restored by the expression of beta(3) containing Y747F or Y759F mutations but not by wild type beta(3) integrin. Thus, phosphorylation of the cytoplasmic domain of beta(3) is a negative regulator of alpha(v)beta(3)-fibronectin binding strength.
Datta
Anirban
A
Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6076, USA.
Huber
Francois
F
Boettiger
David
D
D015703:Antigens, CD / Q000378:metabolism*; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039661:Integrin beta3; D008024:Ligands; D010766:Phosphorylation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism
D015703:Antigens, CD; D005353:Fibronectins; D039661:Integrin beta3; D008024:Ligands; D010980:Platelet Membrane Glycoproteins; D019061:src-Family Kinases