Laminin-binding integrin alpha 7 beta 1: functional characterization and expression in normal and malignant melanocytes.
A novel integrin, alpha 7 beta 1, that specifically binds with high affinity to laminin has been identified on melanoma cells. This complex was purified from both human and murine melanoma cells by laminin-affinity chromatography, and the alpha 7 subunit was recovered after gel electrophoresis. N-terminal amino acid sequence analysis of the alpha 7 subunit from both human and mouse cells verifies that this integrin is distinct from other alpha chains in the beta 1 family, although strikingly similar to the alpha 6 subunit. By using specific proteolytically derived fragments of laminin, it was determined that the alpha 7 beta 1 complex binds selectively to the E8 region, which represents part of the long arm of laminin. In contrast, the receptor failed to bind to the P1 fragment, which contains the intersection of the short arms of laminin. Although the alpha 7 beta 1 complex was commonly expressed in melanoma cells, this integrin was not detected in normal melanocytes, suggesting that alpha 7 expression may be associated with malignant transformation. These results establish the existence of a novel integrin that binds to the E8 domain of laminin and appears to mediate cell adhesion to this ligand.
Kramer
R H
RH
Department of Stomatology, University of California, San Francisco 94143.
Vu
M P
MP
Cheng
Y F
YF
Ramos
D M
DM
Timpl
R
R
Waleh
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D017474:Receptors, Laminin; D014407:Tumor Cells, Cultured / Q000378:metabolism
D016023:Integrins; D007797:Laminin; D011971:Receptors, Immunologic; D017474:Receptors, Laminin