2007
DOI: 10.1182/blood-2007-03-077628
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Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin–mediated human T-cell adhesion

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Cited by 119 publications
(126 citation statements)
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“…Downstream of calcium signaling, Rap1 from the Ras family of small GTPases plays an important role in ␤2 integrin affinity regulation and adhesion, but this has not been established for ␣4␤1 integrin (4,35). It has been shown that Rap1 mediates phorbol-ester (phorbol 12-myristate 13-acetate)-stimulated adhesion to FN, but Rap1 does not mediate SDF-1␣-stimulated affinity up-regulation of ␣4␤1 integrin for VCAM-1 or adhesion to VCAM-1 after SDF-1␣ or phorbol 12-myristate 13-acetate stimulation (36,37). However, Rap1 specifically activates B-Raf, not Raf-1, and precedence for RAF family members in adhesion regulation was provided by studies demonstrating that H-Ras activation of Raf-1 suppressed integrin activation in CHO cells, but there were conflicting results concerning whether the suppression was independent of ERK (38 -42).…”
Section: Discussionmentioning
confidence: 99%
“…Downstream of calcium signaling, Rap1 from the Ras family of small GTPases plays an important role in ␤2 integrin affinity regulation and adhesion, but this has not been established for ␣4␤1 integrin (4,35). It has been shown that Rap1 mediates phorbol-ester (phorbol 12-myristate 13-acetate)-stimulated adhesion to FN, but Rap1 does not mediate SDF-1␣-stimulated affinity up-regulation of ␣4␤1 integrin for VCAM-1 or adhesion to VCAM-1 after SDF-1␣ or phorbol 12-myristate 13-acetate stimulation (36,37). However, Rap1 specifically activates B-Raf, not Raf-1, and precedence for RAF family members in adhesion regulation was provided by studies demonstrating that H-Ras activation of Raf-1 suppressed integrin activation in CHO cells, but there were conflicting results concerning whether the suppression was independent of ERK (38 -42).…”
Section: Discussionmentioning
confidence: 99%
“…Furthermore, the published data suggest that PLC activation seems to be a key event in GPCR-mediated integrin activation (32,37). The available data indicate that the involved GEFs and GTPases not only vary among cell types but also among signaling pathways targeting different integrins.…”
Section: Leukocyte Recruitmentmentioning
confidence: 99%
“…During rolling, however, leukocytes pick up inflammatory signals presented on the endothelial cells that may trigger arrest (31). On a cellular level, leukocyte arrest is mediated by the activation of GPCRs that mediate activation of integrins to their extended, high-affinity conformation, resulting in binding of ligands such as ICAM-1 or VCAM-1 (32).…”
Section: Leukocyte Recruitmentmentioning
confidence: 99%
“…The Rap-GEFs RasGRP2 and RasGRP3 have 2 Ca 21 -binding domains as well as the GEF domain, 38 suggesting that RasGRPs could link Rap1 to Ca 21 signaling. [39][40][41] We therefore investigated the contribution of these Rap-GEFs to MEC1 cell migration. Depletion of RasGRP2 ( Figure 5A; supplemental Figure 4A) reduced basal migration in MEC1-C38H but not MEC1-GFP cells ( Figure 5B; supplemental Figure 4B).…”
Section: Cell Migration In Cd38-expressing Cells Is Dependent On Thementioning
confidence: 99%