Tissue transglutaminase, coagulation factor XIII, and the pro-polypeptide of von Willebrand factor are all ligands for the integrins α9β1 and α4β1

Abstract

We previously reported that MOLT-3 human lymphocyte-like leukemia cells adhere to tissue-type transglutaminase (tTG) through the integrin α4β1. We now report that G-361 human melanoma cells also adhere to tTG, although they do not express α4β1. G-361 cells utilize two additional integrins, α9β1 and α5β1 to adhere to tTG. Furthermore, blood coagulation factor XIII (FXIII), another member of the transglutaminase family that is highly homologous to tTG, and propolypeptide of von Willebrand factor (pp-vWF) also promoted cell adhesion through α9β1 or α4β1 in G-361 or MOLT-3 cells, respectively. In the case of pp-vWF, α9β1 and α4β1 both bind to the same site, comprised of 15 amino acid residues and designated T2-15. Moreover, SW480 human colon cancer cells stably transfected to express α9β1, but not mock transfectants, adhered to tTG, FXIII, pp-vWF, and T2-15/ bovine serum albumin conjugate. These data identify tTG, FXIII, and pp-vWF as shared ligands for the integrins α9β1. and α4β1. This report is the first to unambiguously show that these two integrins share the same cell adhesion site within one protein and provides strong support for classifying α9β1- and α4-integrins as functionally related members of an integrin subfamily.