Small GTPases and LFA-1 reciprocally modulate adhesion and signaling.
Leukocyte-function-associated antigen-1 (LFA-1) is an integrin that is critical for T-cell adhesion and immunologic responses. As a transmembrane receptor and adhesion molecule, LFA-1 signals bidirectionally, whereby information about extracellular ligands is passed outside-in while cellular activat...
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| Fformat: | Journal article |
| Iaith: | English |
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2007
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| _version_ | 1826287137549451264 |
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| author | Mor, A Dustin, M Philips, MR |
| author_facet | Mor, A Dustin, M Philips, MR |
| author_sort | Mor, A |
| collection | OXFORD |
| description | Leukocyte-function-associated antigen-1 (LFA-1) is an integrin that is critical for T-cell adhesion and immunologic responses. As a transmembrane receptor and adhesion molecule, LFA-1 signals bidirectionally, whereby information about extracellular ligands is passed outside-in while cellular activation is transmitted inside-out to the adhesive ectodomain. Here, we review the role of small guanosine triphosphatases (GTPases) in LFA-1 signaling. Rap1, a Ras-related GTPase, appears to be central to LFA-1 function. Rap1 is regulated by receptor signaling [e.g. T-cell receptor (TCR), CD28, and cytotoxic T-lymphocyte antigen-4 (CTLA-4)] and by adapter proteins [e.g. adhesion and degranulation-promoting adapter protein (ADAP) and Src kinase-associated phosphoprotein of 55 kDa (SKAP-55)]. Inside-out signaling flows through Rap1 to regulator of adhesion and cell polarization enriched in lymphoid tissues (RAPL) and Rap1-GTP interacting adapter molecule (RIAM) that act in conjunction with the cytoskeleton on the cytosolic domain of LFA-1 to increase adhesion of the ectodomain. Outside-in signaling also relies on small GTPases such as Rho proteins. Vav-1, a guanine nucleotide exchange factor for Rho proteins, is activated as a consequence of LFA-1 engagement. Jun-activating binding protein-1 (JAB-1) and cytohesin-1 have been implicated as possible outside-in signaling intermediates. We have recently shown that Ras is also downstream of LFA-1 engagement: LFA-1 signaling through phospholipase D (PLD) to RasGRP1 was required for Ras activation on the plasma membrane following stimulation of TCR. |
| first_indexed | 2024-03-07T01:54:07Z |
| format | Journal article |
| id | oxford-uuid:9b23535c-ed4d-445a-aa0d-776e1bc964e9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:54:07Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:9b23535c-ed4d-445a-aa0d-776e1bc964e92022-03-27T00:26:31ZSmall GTPases and LFA-1 reciprocally modulate adhesion and signaling.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9b23535c-ed4d-445a-aa0d-776e1bc964e9EnglishSymplectic Elements at Oxford2007Mor, ADustin, MPhilips, MRLeukocyte-function-associated antigen-1 (LFA-1) is an integrin that is critical for T-cell adhesion and immunologic responses. As a transmembrane receptor and adhesion molecule, LFA-1 signals bidirectionally, whereby information about extracellular ligands is passed outside-in while cellular activation is transmitted inside-out to the adhesive ectodomain. Here, we review the role of small guanosine triphosphatases (GTPases) in LFA-1 signaling. Rap1, a Ras-related GTPase, appears to be central to LFA-1 function. Rap1 is regulated by receptor signaling [e.g. T-cell receptor (TCR), CD28, and cytotoxic T-lymphocyte antigen-4 (CTLA-4)] and by adapter proteins [e.g. adhesion and degranulation-promoting adapter protein (ADAP) and Src kinase-associated phosphoprotein of 55 kDa (SKAP-55)]. Inside-out signaling flows through Rap1 to regulator of adhesion and cell polarization enriched in lymphoid tissues (RAPL) and Rap1-GTP interacting adapter molecule (RIAM) that act in conjunction with the cytoskeleton on the cytosolic domain of LFA-1 to increase adhesion of the ectodomain. Outside-in signaling also relies on small GTPases such as Rho proteins. Vav-1, a guanine nucleotide exchange factor for Rho proteins, is activated as a consequence of LFA-1 engagement. Jun-activating binding protein-1 (JAB-1) and cytohesin-1 have been implicated as possible outside-in signaling intermediates. We have recently shown that Ras is also downstream of LFA-1 engagement: LFA-1 signaling through phospholipase D (PLD) to RasGRP1 was required for Ras activation on the plasma membrane following stimulation of TCR. |
| spellingShingle | Mor, A Dustin, M Philips, MR Small GTPases and LFA-1 reciprocally modulate adhesion and signaling. |
| title | Small GTPases and LFA-1 reciprocally modulate adhesion and signaling. |
| title_full | Small GTPases and LFA-1 reciprocally modulate adhesion and signaling. |
| title_fullStr | Small GTPases and LFA-1 reciprocally modulate adhesion and signaling. |
| title_full_unstemmed | Small GTPases and LFA-1 reciprocally modulate adhesion and signaling. |
| title_short | Small GTPases and LFA-1 reciprocally modulate adhesion and signaling. |
| title_sort | small gtpases and lfa 1 reciprocally modulate adhesion and signaling |
| work_keys_str_mv | AT mora smallgtpasesandlfa1reciprocallymodulateadhesionandsignaling AT dustinm smallgtpasesandlfa1reciprocallymodulateadhesionandsignaling AT philipsmr smallgtpasesandlfa1reciprocallymodulateadhesionandsignaling |