Alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule.
The avidity of integrin adhesion receptors for extracellular ligands is subject to dynamic regulation by intracellular programs that have yet to be elucidated. We describe here a protein, cytohesin-1, which specifically interacts with the intracellular portion of the integrin beta 2 chain (CD18). The molecule shows homology to the yeast SEC7 gene product and bears a pleckstrin homology (PH) domain. Overexpression of either the full-length cytohesin-1 or the SEC7 domain induces beta 2 integrin-dependent binding of Jurkat cells to ICAM-1, whereas expression of the isolated cytohesin-1 PH domain inhibits T cell receptor-stimulated adhesion. Similar inhibition is not exhibited by PH domains taken from other proteins, showing that the interaction is specific and that individual PH domains are capable of discriminating between alternative targets.
Kolanus
W
W
Laboratorium für Molekulare Biologie, Genzentrum der Universität München, Federal Republic of Germany.
Nagel
W
W
Schiller
B
B
Zeitlmann
L
L
Godar
S
S
Stockinger
H
H
Seed
B
B
D000595:Amino Acid Sequence; D001483:Base Sequence; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D002460:Cell Line / Q000737:chemistry; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors; D019073:HT29 Cells / Q000502:physiology; D006367:HeLa Cells / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007938:Leukemia; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics; D012680:Sensitivity and Specificity; D014616:Vaccinia virus / Q000235:genetics; D015003:Yeasts / Q000737:chemistry / Q000235:genetics
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D020662:Guanine Nucleotide Exchange Factors; D016169:Lymphocyte Function-Associated Antigen-1; D011994:Recombinant Proteins; C100723:cytohesin-1; D018799:Intercellular Adhesion Molecule-1