Tissue transglutaminase, coagulation factor XIII, and the pro-polypeptide of von Willebrand factor are all ligands for the integrins alpha 9beta 1 and alpha 4beta 1.
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.
Takahashi
H
H
Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
Isobe
T
T
Horibe
S
S
Takagi
J
J
Yokosaki
Y
Y
Sheppard
D
D
Saito
Y
Y
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D003110:Colonic Neoplasms; D005176:Factor XIII / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D039482:Integrin alpha5; D016023:Integrins / Q000378:metabolism*; D007945:Leukemia, Lymphoid; D008024:Ligands; D008545:Melanoma / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011498:Protein Precursors / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D011503:Transglutaminases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014841:von Willebrand Factor / Q000378:metabolism*
D015703:Antigens, CD; D039041:Integrin alpha4beta1; D039482:Integrin alpha5; D016023:Integrins; D008024:Ligands; D011498:Protein Precursors; D016201:Receptors, Lymphocyte Homing; C113256:integrin alpha 9 beta 1; D014841:von Willebrand Factor; C067003:von Willebrand factor propolypeptide; D005176:Factor XIII; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins