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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
33
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pubmed:dateCreated |
2002-8-12
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pubmed:abstractText |
In T-lymphocytes the Ras-like small GTPase Rap1 plays an essential role in stimulus-induced inside-out activation of integrin LFA-1 (alpha(L)beta(2)) and VLA-4 (alpha(4)beta(1)). Here we show that Rap1 is also involved in the direct activation of these integrins by divalent cations or activating antibodies. Inhibition of Rap1 either by Rap GTPase-activating protein (RapGAP) or the Rap1 binding domain of RalGDS abolished both Mn(2+)- and KIM185 (anti-LFA-1)-induced LFA-1-mediated cell adhesion to intercellular adhesion molecule 1. Mn(2+)- and TS2/16 (anti-VLA-4)-induced VLA-4-mediated adhesion were inhibited as well. Interestingly, both Mn(2+), KIM185 and TS2/16 failed to induce elevated levels of Rap1GTP. These findings indicate that available levels of GTP-bound Rap1 are required for the direct activation of LFA-1 and VLA-4. Pharmacological inhibition studies demonstrated that both Mn(2+)- and KIM185-induced adhesion as well as Rap1-induced adhesion require intracellular calcium but not signaling activity of the MEK-ERK pathway. Moreover, functional calmodulin signaling was shown to be a prerequisite for Rap1-induced adhesion. From these results we conclude that in addition to stimulus-induced inside-out activation of integrins, active Rap1 is required for cell adhesion induced by direct activation of integrins LFA-1 and VLA-4. We suggest that Rap1 determines the functional availability of integrins for productive binding to integrin ligands.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD18,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD29,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Cations, Divalent,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha4beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Integrins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Function-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Manganese,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lymphocyte Homing,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/rap1 GTP-Binding Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
29468-76
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12171996-Antibodies,
pubmed-meshheading:12171996-Antigens, CD18,
pubmed-meshheading:12171996-Antigens, CD29,
pubmed-meshheading:12171996-Calcium,
pubmed-meshheading:12171996-Calmodulin,
pubmed-meshheading:12171996-Cations, Divalent,
pubmed-meshheading:12171996-Cell Adhesion,
pubmed-meshheading:12171996-Humans,
pubmed-meshheading:12171996-Integrin alpha4beta1,
pubmed-meshheading:12171996-Integrins,
pubmed-meshheading:12171996-Intercellular Adhesion Molecule-1,
pubmed-meshheading:12171996-Jurkat Cells,
pubmed-meshheading:12171996-K562 Cells,
pubmed-meshheading:12171996-Lymphocyte Function-Associated Antigen-1,
pubmed-meshheading:12171996-Manganese,
pubmed-meshheading:12171996-Receptors, Lymphocyte Homing,
pubmed-meshheading:12171996-Tetradecanoylphorbol Acetate,
pubmed-meshheading:12171996-Vascular Cell Adhesion Molecule-1,
pubmed-meshheading:12171996-rap1 GTP-Binding Proteins
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pubmed:year |
2002
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pubmed:articleTitle |
The small GTPase Rap1 is required for Mn(2+)- and antibody-induced LFA-1- and VLA-4-mediated cell adhesion.
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pubmed:affiliation |
Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Utrecht University, Universiteitsweg 100, P. O. Box 85060, 3508 AB Utrecht, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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