ICAP-1, a novel beta1 integrin cytoplasmic domain-associated protein, binds to a conserved and functionally important NPXY sequence motif of beta1 integrin.
The cytoplasmic domains of integrins are essential for cell adhesion. We report identification of a novel protein, ICAP-1 (integrin cytoplasmic domain- associated protein-1), which binds to the 1 integrin cytoplasmic domain. The interaction between ICAP-1 and beta1 integrins is highly specific, as demonstrated by the lack of interaction between ICAP-1 ... and the cytoplasmic domains of other beta integrins, and requires a conserved and functionally important NPXY sequence motif found in the COOH-terminal region of the beta1 integrin cytoplasmic domain. Mutational studies reveal that Asn and Tyr of the NPXY motif and a Val residue located NH2-terminal to this motif are critical for the ICAP-1 binding. Two isoforms of ICAP-1, a 200-amino acid protein (ICAP-1alpha) and a shorter 150-amino acid protein (ICAP-1beta), derived from alternatively spliced mRNA, are expressed in most cells. ICAP-1alpha is a phosphoprotein and the extent of its phosphorylation is regulated by the cell-matrix interaction. First, an enhancement of ICAP-1alpha phosphorylation is observed when cells were plated on fibronectin-coated but not on nonspecific poly-L-lysine-coated surface. Second, the expression of a constitutively activated RhoA protein that disrupts the cell-matrix interaction results in dephosphorylation of ICAP-1alpha. The regulation of ICAP-1alpha phosphorylation by the cell-matrix interaction suggests an important role of ICAP-1 during integrin-dependent cell adhesion.
Mesh Terms:
3T3 Cells, Alternative Splicing, Amino Acid Sequence, Animals, Antigens, CD29, Binding Sites, Carrier Proteins, Cell Line, Cloning, Molecular, Conserved Sequence, Fibronectins, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Macromolecular Substances, Membrane Proteins, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, Phosphorylation, Point Mutation, Polylysine, Polymerase Chain Reaction, RNA, Messenger, Rats, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid
3T3 Cells, Alternative Splicing, Amino Acid Sequence, Animals, Antigens, CD29, Binding Sites, Carrier Proteins, Cell Line, Cloning, Molecular, Conserved Sequence, Fibronectins, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Macromolecular Substances, Membrane Proteins, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, Phosphorylation, Point Mutation, Polylysine, Polymerase Chain Reaction, RNA, Messenger, Rats, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid
J. Cell Biol.
Date: Sep. 08, 1997
PubMed ID: 9281591
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