Regulation of p56lck kinase expression and control of DNA synthesis in activated human B lymphocytes.
In this study, we analyzed the expression and regulation of src kinase p56lck expression during human B lymphocyte activation. We show that upon mitogenic stimulation with anti-IgM antibodies and interleukin-2, specific mRNA for p56lck becomes detectable in B cells after 24 h of activation and is followed by an increase in p56lck protein expression on days 2 and 3. This up-regulation is specific for p56lck since expression of other src kinases such as fyn, lyn, or yes was not modified. Furthermore, immune complex kinase assays show that p56lck protein expressed on day 2 is associated with kinase activity. Experiments using lck-specific antisense oligonucleotides show that the G0-G1 transition does not require p56lck, whereas DNA synthesis is dependent upon its expression. Thus, our data demonstrate that p56lck expression is up-regulated during human B cell stimulation and this kinase plays an important role during the control of late steps of B lymphocyte activation such as S phase entry.
Taieb
J
J
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 131, Clamart, France.
Vitte-Mony
I
I
Auffredou
M T
MT
Dorseuil
O
O
Gacon
G
G
Bertoglio
J
J
Vazquez
A
A
D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D014066:Palatine Tonsil; D010835:Phytohemagglutinins; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D011519:Proto-Oncogenes; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D007376:Interleukin-2; D016376:Oligonucleotides, Antisense; D010835:Phytohemagglutinins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012313:RNA; D004247:DNA; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D013936:Thymidine