International Immunology, Vol. 11, No. 7, 1085-1092,
July 1999
© 1999 Japanese Society for Immunology
CD44 signaling through p56lck involves lateral association with CD4 in human CD4+ T cells
Dipartimento di Scienze Mediche, University `A. Avogadro' of Eastern Piedmont, via Solaroli 17, 28100 Novara, Italy
1 Dipartimento di Medicina Clinica, Patologia e Farmacologia, Sezione di Ematologia, University of Perugia, Policlinico Monteluce, 06122 Perugia, Italy
Correspondence to: U. Dianzani
CD44 is a family of mucin-like membrane proteins generated by alternative splicing of several exons, and participate in T cell adhesion and activation. CD44-mediated signaling involves activation of p56lck and leads to ZAP-70 phosphorylation. The aim of the present study was to identify the signaling pathways that follow CD44-triggered ZAP-70 phosphorylation and the molecular mechanisms underlying the CD44 interaction with p56lck. We found that CD44 cross-linking by mAb in CD4+ peripheral blood T cells promotes formation of a trimeric complex of Grb2, phospholipase (PLC)-
1 and a 36–38 kDa phosphoprotein, and the activation of PLC-1. The amount of inositol triphosphate and the time kinetics of its generation were comparable to those following CD3 cross-linking. Co-capping, co-immunoprecipitation and fluorescence resonance energy transfer experiments showed that CD44 associates with CD4 and CD3 on the cell surface. This association suggests functional interplay between the CD4–TCR complex and CD44. In line with this possibility, we found that CD4 triggering by gp120, a natural ligand of CD4, potentiates CD44-mediated adhesion to hyaluronic acid. Moreover, Ca2+ mobilization induced by CD44 cross-linking by mAb was higher in a subclone of the HUT78 cell line expressing CD4 than in a non-expressing subclone.
Keywords: adhesion, co-stimulation, phospholipase C
Transmitting editor: L. Moretta
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