ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via interaction with the alphavbeta3 integrin through an RGD-independent mechanism.
ADAM 23 (a disintegrin and metalloproteinase domain)/MDC3 (metalloprotease, disintegrin, and cysteine-rich domain) is a member of the disintegrin family of proteins expressed in fetal and adult brain. In this work we show that the disintegrin-like domain of ADAM 23 produced in Escherichia coli and immobilized on culture dishes promotes attachment of different human cells of neural origin, such as neuroblastoma cells (NB100 and SH-S(y)5(y)) or astrocytoma cells (U373 and U87 MG). Analysis of ADAM 23 binding to integrins revealed a specific interaction with alphavbeta3, mediated by a short amino acid sequence present in its putative disintegrin loop. This sequence lacks any RGD motif, which is a common structural determinant supporting alphavbeta3-mediated interactions of diverse proteins, including other disintegrins. alphavbeta3 also supported adhesion of HeLa cells transfected with a full-length cDNA for ADAM 23, extending the results obtained with the recombinant protein containing the disintegrin domain of ADAM 23. On the basis of these results, we propose that ADAM 23, through its disintegrin-like domain, may function as an adhesion molecule involved in alphavbeta3-mediated cell interactions occurring in normal and pathological processes, including progression of malignant tumors from neural origin.
Cal
S
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Departamentos, Instituto Universitario de Oncología, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain.
Freije
J M
JM
López
J M
JM
Takada
Y
Y
López-Otín
C
C
D051722:ADAM Proteins; D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000502:physiology; D003001:Cloning, Molecular; D019483:Disintegrins / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D019030:Receptors, Vitronectin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D019483:Disintegrins; D016023:Integrins; D009419:Nerve Tissue Proteins; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; D051722:ADAM Proteins; C121259:Adam23 protein, mouse; D008666:Metalloendopeptidases