TYROSINE PHOSPHORYLATION OF CD19 IN PRE-B-CELLS AND MATURE B-CELLS

被引:79
作者
CHALUPNY, NJ
KANNER, SB
SCHIEVEN, GL
WEE, SF
GILLILAND, LK
ARUFFO, A
LEDBETTER, JA
机构
[1] The Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, WA 98121
关键词
ACTIVATION; SH2; DOMAIN; SIGNALING;
D O I
10.1002/j.1460-2075.1993.tb05930.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cross-linking of B cell surface immunoglobulins (sIg) results in activation of mature B cells and stimulates a molecular signaling mechanism for antigen-specific B cell expansion and differentiation. This signaling pathway is dependent on tyrosine (Tyr) phosphorylation and results in the activation of sIg-associated src family kinases and p72SYK. Rapid Tyr phosphorylation occurs on multiple protein substrates. Here we show that activation of B cells by cross-linking sIg results in an increase in Tyr phosphorylation of the lineage-restricted B cell surface antigen CD19, and show that it is a major substrate of activated Tyr kinase following sIg stimulation. Lower levels of constitutive CD19 Tyr phosphorylation occurred in most sIg+ mature B cell lines examined and in normal dense tonsillar B cells. We also rind that when CD19 is Tyr-phosphorylated it becomes competent to interact with SH2 domains suggesting a mechanism whereby, following B cell activation, CD19 could be linked to intracellular signaling pathways. In sIg- pre-B cell lines, CD19 was expressed but was not constitutively phosphorylated on tyrosine. Upon CD19 cross-linking, Tyr phosphorylation of CD19 was induced in sIg- pre-B cell lines. CD19 cross-linking also directly induced Tyr phosphorylation of CD19 and other substrates in mature B cells. The ability of CD19 to signal in the absence of sIg expression may provide important stimulation in pre-B cell development.
引用
收藏
页码:2691 / 2696
页数:6
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