title: Molecular cloning of the rat integrin alpha 1-subunit: a receptor for laminin and collagen.
abstract: Integrin heterodimers mediate a variety of adhesive interactions, including neuronal attachment to and process outgrowth on laminin. We report here the cloning and primary sequence of an M-200 kD integrin alpha subunit that associates with the integrin beta 1 subunit to form a receptor for both laminin and collagen. Similarities in ligand-binding specificity, relative molecular mass and NH2-terminal sequence make this a strong candidate for the rat homologue of the alpha subunit of the human integrin VLA-1. The full-length rat alpha 1 cDNAs encode a protein containing a purative signal sequence and a mature polypeptide of 1,152 amino acids, with extracellular, transmembrane and cytoplasmic domains. Several structural features are conserved with other integrin alpha chains, including (a) a sequence motif repeated seven times in the NH2-terminal half; (b) potential Ca2+/Mg2+ binding sites in repeats 5, 6, and 7, and (c) alignment of at least 14 of 23 cysteine residues. This rat alpha 1 sequence also contains a 206-amino acid I domain, inserted between repeats 2 and 3, that is homologous to I domains found in the same position in the alpha subunits of several integrins (VLA-2, Mac-1, LFA-1, p150). The rat alpha 1 and human VLA-2 apha subunits share greater than 50% sequence identity in the seven repeats and I domain, suggesting that these sequence identities may underlie some of their similar ligand-binding specificities. However, the rat integrin alpha 1 subunit has several unique features, including a 38-residue insert between two Ca2+/Mg2+ binding domains, and a divergent 15-residue cytoplasmic sequence, that may potentially account for unique functions of this integrin.
authors.affiliation: Department of Physiology, University of California, San Francisco 94143-0724.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ignatius
authors.forename: T H
authors.initials: TH
authors.lastname: Large
authors.forename: M
authors.initials: M
authors.lastname: Houde
authors.forename: J W
authors.initials: JW
authors.lastname: Tawil
authors.forename: A
authors.initials: A
authors.lastname: Barton
authors.forename: F
authors.initials: F
authors.lastname: Esch
authors.forename: S
authors.initials: S
authors.lastname: Carbonetto
authors.forename: L F
authors.initials: LF
authors.lastname: Reichardt
mesh_terms: D000310:Adrenal Gland Neoplasms; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular / Q000379:methods; D003094:Collagen / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D015723:Gene Library; D006801:Humans; D016023:Integrins / Q000235:genetics* / Q000378:metabolism; D007797:Laminin / Q000378:metabolism*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015345:Oligonucleotide Probes; D010673:Pheochromocytoma; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
chemical_list: D004273:DNA, Neoplasm; D016023:Integrins; D007797:Laminin; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D003094:Collagen