c-Src tyrosine kinase co-associates with and phosphorylates signal transducer and activator of transcription 5b which mediates the proliferation of normal human B lymphocytes

• Published in: Clinical and experimental immunology 2009-06, Vol.156 (3), p.419-427
• Main Authors: Cayer, M.-P, Proulx, M, Ma, X.-Z, Sakac, D, Giguère, J.-F, Drouin, M, Néron, S, Branch, D.R, Jung, D
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; adenovirus; Analytical, structural and metabolic biochemistry; B-Lymphocytes - immunology; Biological and medical sciences; c-Src; Cell Proliferation; Cells, Cultured; cellular proliferation; Fundamental and applied biological sciences. Psychology; human B lymphocytes; Humans; phosphorylation; Phosphorylation - immunology; Signal Transduction - immunology; src-Family Kinases - immunology; STAT5; STAT5 Transcription Factor - immunology; Transduction, Genetic; Translational Studies
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2009.03917.x

c-Src is the normal human cellular protein homologue of the viral oncogene v-src. c-Src activity was reported recently to increase in CD40-activated human B lymphocytes, suggesting its involvement in proliferation. To elucidate the exact role of c-Src in this process, we investigated the effects of c-Src over-expression on normal B lymphocyte growth. B lymphocytes purified from human peripheral blood were infected with Ad5/F35 vector encoding either a constitutively active c-Src (c-Src/dominant-positive) or a dominant-negative c-Src (c-Src/DN). Little variation of B lymphocytes expansion could be observed between control enhanced yellow fluorescent protein and c-Src/dominant-positive-infected cells. In contrast, over-expression of c-Src/DN results in a 40% inhibition of B lymphocyte expansion. These results suggest that DN c-Src may compete with endogenous c-Src, resulting in partial inhibition of a transcriptional pathway involved in B lymphocyte proliferation. We demonstrate further that c-Src can phosphorylate signal transducer and activator of transcription 5b (STAT5b) on tyrosine 699 and that c-Src and STAT5b co-associate during B lymphocyte proliferation. These results confirm an important role for c-Src in the expansion of normal human B lymphocytes in vitro, in which c-Src may regulate STAT5b in the intracellular signalling pathway important for the proliferation of normal human B lymphocytes.