Role of src-like protooncogenes in lymphocyte proliferation.

Cross-linking of membrane-bound immunoglobulins, which are B cell antigen receptors, causes proliferation and differentiation of B cells or the inhibition of their growth. The receptor-mediated signalling involves tyrosine phosphorylation of cellular proteins. The Src-like protein-tyrosine kinase Lyn is expressed preferentially in B cells and is an intracytoplasmic constituent of the B cell antigen receptor complex. Cross-linking of membrane-bound immunoglobulin M with antibody induced rapid increases in the kinase activities of Lyn and Lyn-associated phosphatidylinositol-3 kinase. Cross-linking of B-cell antigen receptor also induced association of Lyn with an 85 kDa non-catalytic subunit of phosphatidylinositol-3 kinase. Thus, Lyn is functionally associated with membrane-bound immunoglobulin M, and seems to participate in B cell antigen receptor-mediated signalling. On the other hand, accumulating evidence shows that Fyn and Lck are involved in T-cell activation. Co-immunoprecipitation experiments showed that Fyn was physically associated with T cell antigen receptor-CD3 complex. Transient expression of actively mutated Fyn, having Phe-528 instead of Tyr-528, in Jurkat T cells stimulated the fos promoter and serum response element (SRE), suggesting that the Fyn kinase stimulates c-fos expression through SRE. An analogous set of experiments showed that introduction of the active Fyn alone had little effect on IL-2 promoter. However, it could stimulate transcription from this promoter when transfected cells were stimulated by a combination of Concanavalin A (ConA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). Under the same conditions, normal Lck and Lyn could not stimulate IL-2 promoter.