J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/09/1149/09 $2.00
Volume 138, Number 5, September 8, 1997 1149-1157

ICAP-1, a Novel ₁ Integrin Cytoplasmic Domain-associated Protein, Binds to a Conserved and Functionally Important NPXY Sequence Motif of ₁ Integrin

David D. Chang, Carol Wong, Healy Smith, and Jenny Liu

Department of Medicine, and Department of Microbiology and Immunology, University of California, Los Angeles, California 90095

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 ₁ integrins is highly specific, as demonstrated by the lack of interaction between ICAP-1 and the cytoplasmic domains of other  integrins, and requires a conserved and functionally important NPXY sequence motif found in the COOH-terminal region of the ₁ 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-1) and a shorter 150-amino acid protein (ICAP-1), derived from alternatively spliced mRNA, are expressed in most cells. ICAP-1 is a phosphoprotein and the extent of its phosphorylation is regulated by the cell-matrix interaction. First, an enhancement of ICAP-1 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-1. The regulation of ICAP-1 phosphorylation by the cell-matrix interaction suggests an important role of ICAP-1 during integrin-dependent cell adhesion.

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