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.
Yamamoto
T
T
Institute of Medical Science, University of Tokyo, Japan.
Yamanashi
Y
Y
Takeuchi
M
M
Fusaki
N
N
Uchiumi
F
F
Katagiri
T
T
Semba
K
K
Toyoshima
K
K
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D005786:Gene Expression Regulation; D016762:Genes, fos; D016391:Genes, src / Q000502:physiology*; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D010766:Phosphorylation; D010770:Phosphotransferases / Q000032:analysis; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D019061:src-Family Kinases
D007075:Immunoglobulin M; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases