ICAP-1, A NOVEL BETA(1) INTEGRIN CYTOPLASMIC DOMAIN-ASSOCIATED PROTEIN, BINDS TO A CONSERVED AND FUNCTIONALLY IMPORTANT NPXY SEQUENCE MOTIFOF BETA(1) INTEGRIN
Dd. Chang et al., ICAP-1, A NOVEL BETA(1) INTEGRIN CYTOPLASMIC DOMAIN-ASSOCIATED PROTEIN, BINDS TO A CONSERVED AND FUNCTIONALLY IMPORTANT NPXY SEQUENCE MOTIFOF BETA(1) INTEGRIN, The Journal of cell biology, 138(5), 1997, pp. 1149-1157
The cytoplasmic domains of integrins are essential for cell adhesion.
We report identification of a novel protein, ICAP-1 (integrin cytoplas
mic domain-associated protein-1), which binds to the beta(1) integrin
cytoplasmic domain. The interaction between ICAP-1 and pi integrins is
highly specific, as demonstrated by the lack of interaction between I
CAP-1 and the cytoplasmic domains of other beta integrins, and require
s a conserved and functionally important NPXY sequence motif found in
the COOH-terminal region of the beta(1) integrin cytoplasmic domain. M
utational 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 alp
ha) and a shorter 150-amino acid protein (ICAP-1 beta), derived from a
lternatively spliced mRNA, are expressed in most cells. ICAP-1 alpha i
s a phosphoprotein and the extent of its phosphorylation is regulated
by the cell-matrix interaction. First, an enhancement of ICAP-1 alpha
phosphorylation is observed when cells were plated on fibronectin-coat
ed but not on nonspecific poly-L-lysine-coated surface. Second, the ex
pression of a constitutively activated RhoA protein that disrupts the
cell-matrix interaction results in dephosphorylation of ICAP-1 alpha.
The regulation of ICAP-1 alpha phosphorylation by the cell-matrix inte
raction suggests an important role of ICAP-1 during integrin-dependent
cell adhesion.