Interaction of the integrin beta1 cytoplasmic domain with ICAP-1 protein.
In a yeast two-hybrid screen, a protein named ICAP-1 (beta1 integrin cytoplasmic domain associated protein) associated with the integrin beta1 cytoplasmic tail but not with tails from three other integrin beta subunits (beta2, beta3, and beta5) or from seven different alpha subunits. Likewise in human cells, ICAP-1 associated specifically with the beta1 but not beta2, beta3, or beta5 tails. The carboxyl-terminal 14 amino acids of beta1 were critical for ICAP-1 interaction. ICAP-1 is a ubiquitously expressed protein of 27 and 31 kDa, with the smaller form being preferentially solubilized by Triton X-100. Phosphorylation of both 27- and 31-kDa forms was constitutive but was increased by 1.5-2-fold upon cell spreading on fibronectin, compared with poly-L-lysine. Also, ICAP-1 contributes to beta1 integrin-dependent migration because (i) ICAP-1 transfection markedly increased chemotactic migration of COS7 cells through fibronectin-coated but not vitronectin-coated porous filters, and (ii) support of beta1-dependent cell migration (in Chinese hamster ovary cells transfected with various wild type and mutant beta1 forms) correlated with ICAP-1 association. In summary, ICAP-1 (i) associates specifically with beta1 integrins, (ii) is phosphorylated upon beta1 integrin-mediated adhesion, and (iii) may regulate beta1-dependent cell migration.
Zhang
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Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Hemler
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D003001:Cloning, Molecular; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D018076:DNA, Complementary; D006801:Humans; D019012:Integrin beta1 / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018076:DNA, Complementary; C108257:ITGB1BP1 protein, human; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins