Tissue Transglutaminase, Coagulation Factor XIII, and the Pro-polypeptide of von Willebrand Factor Are All Ligands for the Integrins α9β1 and α4β1

Hiroo Takahashi,Takashi Isobe,Shiho Horibe,Junichi Takagi,Yasuyuki Yokosaki,Dean Sheppard,Yuji Saito

doi:10.1074/jbc.m003526200

Hiroo Takahashi, Takashi Isobe + Show 5 more

Open Access

https://doi.org/10.1074/jbc.m003526200

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Abstract

We previously reported that MOLT-3 human lymphocyte-like leukemia cells adhere to tissue-type transglutaminase (tTG) through the integrin alpha(4)beta(1). We now report that G-361 human melanoma cells also adhere to tTG, although they do not express alpha(4)beta(1). G-361 cells utilize two additional integrins, alpha(9)beta(1) and alpha(5)beta(1) 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 alpha(9)beta(1) or alpha(4)beta(1) in G-361 or MOLT-3 cells, respectively. In the case of pp-vWF, alpha(9)beta(1) and alpha(4)beta(1) 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 alpha(9)beta(1), 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 alpha(9)beta(1) and alpha(4)beta(1). 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 alpha(9)beta(1-) and alpha(4)-integrins as functionally related members of an integrin subfamily.

Highlights

Integrins are a family of heterodimeric transmembrane receptors that mediate cell-extracellular matrix and cell-cell interactions and play important roles in a wide variety of cellular events [1,2,3,4,5,6]
We previously reported that MOLT-3 human lymphocyte-like leukemia cells adhere to tissue-type transglutaminase through the integrin ␣4␤1
G-361 Human Melanoma Cells Adhere to type transglutaminase (tTG) through ␤1Integrin(s) but Not ␣4␤1—In a previous study [31], we reported that tTG promoted cell adhesion of MOLT-3 cells mediated by the integrin ␣4␤1

Summary

Introduction

Integrins are a family of heterodimeric transmembrane receptors that mediate cell-extracellular matrix and cell-cell interactions and play important roles in a wide variety of cellular events [1,2,3,4,5,6]. We previously reported that MOLT-3 human lymphocyte-like leukemia cells adhere to tissue-type transglutaminase (tTG) through the integrin ␣4␤1. SW480 human colon cancer cells stably transfected to express ␣9␤1, but not mock transfectants, adhered to tTG, FXIII, pp-vWF, and T2–15/ bovine serum albumin conjugate.

Results

Conclusion