Syndecan-1 signals independently of beta 1 integrins during Raji cell spreading

Syndecan-1-expressing Raji lymphoid cells (Raji-S1 cells) bind and spread r apidly when attaching to matrix ligands that contain heparan sulfate-bindin g domains. However, these ligands also contain binding sites for integrins, which are widely known to signal, raising the question of whether the prot eoglycan core protein participates in generation of the signal for spreadin g. To address this question, the spreading of the Raji-S1 cells is examined on ligands specific for either beta 1 integrins, known to be present on th e Raji cells, or the syndecan-1 core protein. The cells adhere and spread o n invasin, a ligand that activates beta 1 integrins, the IIICS fragment of fibronectin, which is a specific ligand for the alpha 4 beta 1 integrin, or mAb281.2, an antibody specific for the syndecan-1 core protein. The signal ing resulting from adhesion to the syndecan-specific antibody appears integ rin independent as (i) the morphology of the cells spreading on the antibod y is distinct from spreading initiated by the integrins alone; (ii) spreadi ng on the syndecan or integrin ligands is affected differently by the kinas e inhibitors tyrphostin 25, genistein, and staurosporine; and (iii) spreadi ng on the syndecan-specific antibody is not disrupted by blocking beta 1 in tegrin activation with mAb13, a beta 1 inhibitory antibody. These data demo nstrate that ligation of syndecan-1 initiates intracellular signaling and s uggest that this signaling occurs when cells expressing syndecan-1 adhere t o matrix ligands containing heparan sulfate-binding domains. (C) 2000 Acade mic Press.