The alpha 4 beta 1 fibronectin ligands CS-1, HEP II, and RGD induce different intracellular events in B lymphoid cells. Comparison with the effects of the endothelial ligand VCAM-1

被引:16
作者
DominguezJimenez, C [1 ]
SanchezAparicio, P [1 ]
Albar, JP [1 ]
GarciaPardo, A [1 ]
机构
[1] CSIC,CTR NACL BIOTECNOL,DEPT INMUNOL,MADRID 28049,SPAIN
关键词
B lymphocytes; alpha; 4; beta; 1; integrin; cell signaling; fibronectin; cytoskeleton;
D O I
10.3109/15419069609010770
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The lymphocyte integrin alpha 4 beta 1 is the receptor for the Hep II domain and CS-1 site in fibronectin (Fn) as well as for VCAM-1. We recently showed that upon activation with anti-beta 1 mAb TS2/16, alpha 4 beta 1 also recognizes the RGD Fn sequence. To determine the physiological role of these multiple interactions, we have now studied some intracellular events induced by ''resting'' and activated alpha 4 beta 1 binding to its different ligands. Analyses of actin and tubulin reorganization upon adhesion of B lymphoid cells to Fn fragments or VCAM-1 showed that VCAM-1, a 38 kDa fragment (Hep II+CS-1), and the CS-1 synthetic peptide induced formation of transient cytoplasmic projections; however, cells attached to a 58 kDa (Hep II) or 80 kDa (RGD) fragments remained rounded. Using transfilter assays, we showed that VCAM-1, 38 kDa and CS-1 also induced dose-dependent B cell migration mediated by alpha 4 beta 1. Furthermore, these three ligands, but not the 80 kDa fragment or a synthetic peptide (H1) containing a sequence from Hep II shown to bind alpha 4 beta 1, induced tyrosine phosphorylation of a 110 kDa protein. Activation of alpha 4 beta 1 with TS2/16 inhibited the cytoplasmic protrusions and cell migration but did not affect the pattern of phosphorylation. Our results indicate that the various alpha 4 beta 1 ligands induce different cellular responses. Most importantly they show that alpha 4 beta 1 interaction with CS-1 is sufficient to trigger intracellular events in B cells. Furthermore, they suggest a regulation by the activation form of the receptor as well as by the ligand in events involving lymphocyte adhesion and migration.
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页码:251 / &
页数:19
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