The GTPase Rap1 regulates phorbol 12-myristate 13-acetate-stimulated but not ligand-induced beta 1 integrin-dependent leukocyte adhesion

Leukocyte migration from bloodstream to tissue requires rapid, coordinated regulation of integrin-dependent adhesion and de-adhesion. In a previous study we demonstrated that inhibition of protein geranylgeranylation inhibited phorbol ester-stimulated avidity modulation of beta(1) integrin in severa...

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Bibliographic Details
Published inThe Journal of biological chemistry Vol. 277; no. 43; p. 40893
Main Authors Liu, Li, Schwartz, Barbara R, Tupper, Joan, Lin, Nancy, Winn, Robert K, Harlan, John M
Format Journal Article
LanguageEnglish
Published United States 25.10.2002
Subjects
Cell Adhesion - physiology
Cytochalasin D - pharmacology
Enzyme Activation
Fibronectins - metabolism
GTPase-Activating Proteins
Humans
Integrin beta1 - physiology
Jurkat Cells
Leukocytes - cytology
Ligands
Nuclear Proteins - metabolism
Phosphorylation
Protein Kinase C - metabolism
rap1 GTP-Binding Proteins - physiology
Tetradecanoylphorbol Acetate - pharmacology
Tyrosine - metabolism
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Summary:Leukocyte migration from bloodstream to tissue requires rapid, coordinated regulation of integrin-dependent adhesion and de-adhesion. In a previous study we demonstrated that inhibition of protein geranylgeranylation inhibited phorbol ester-stimulated avidity modulation of beta(1) integrin in several leukocyte cell lines. Both RhoA and Rap1 require post-translational modification by geranylgeranylation for full function. In this report we identify Rap1, not RhoA, as a critical geranylgeranylated protein mediating phorbol ester-stimulated beta(1) and beta(2) integrin-dependent adhesion of Jurkat cells. Overexpression of the Rap1-specific GTPase-activating protein, SPA-1, or inactivated form of Rap1 (N17Rap1) blocked phorbol ester-stimulated adhesion of Jurkat cells to fibronectin (alpha(4)beta(1)) and ICAM-1 (alpha(L)beta(2)). With high concentrations of fibronectin as ligand, Jurkat cells adhered spontaneously without phorbol ester stimulation. Unlike the phorbol ester-stimulated adhesion, adhesion induced by high density ligand was not dependent upon Rap1 activation or actin cytoskeleton reorganization. Thus, the "inside-out" adhesion signal induced by phorbol ester and the "outside-in" signal induced by high density ligand involve different pathways.
ISSN:0021-9258
1083-351X