Watts J D, Sanghera J S, Pelech S L, Aebersold R
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
J Biol Chem. 1993 Nov 5;268(31):23275-82.
p56lck, a member of the src family of non-receptor protein tyrosine kinases, is expressed almost exclusively in cells of lymphoid origin. Recent evidence has implicated p56lck in a critical role both in T cell development and activation. A variety of T cell stimuli induce a shift in the electrophoretic mobility of p56lck from an apparent molecular mass of 56 kDa (p56lck) to 60 kDa (p60lck). This shift in electrophoretic mobility correlates with an increase in the phosphoserine content of the p60lck. We have shown that both 4 alpha-phorbol 12 beta-myristate acetate and OKT3 treatment of Jurkat cells, as well as 4 alpha-phorbol 12 beta-myristate acetate treatment of 171.CD4 and LSTRA cells, induced phosphorylation of serine-59 on p56lck in vivo, which correlated with the shift to p60lck. We also demonstrated that the same serine residue could be phosphorylated in vitro with mitogen-activated protein kinases and that this event was capable of reducing p56lck activity in vitro. Combined, these data suggest a novel pathway for the in vivo regulation of p56lck activity.
p56lck是非受体蛋白酪氨酸激酶src家族的成员之一，几乎仅在淋巴起源的细胞中表达。最近的证据表明p56lck在T细胞发育和激活中都起着关键作用。多种T细胞刺激可诱导p56lck的电泳迁移率从表观分子量56 kDa（p56lck）转变为60 kDa（p60lck）。这种电泳迁移率的变化与p60lck中磷酸丝氨酸含量的增加相关。我们已经表明，用4α-佛波醇12β-肉豆蔻酸酯乙酸盐和OKT3处理Jurkat细胞，以及用4α-佛波醇12β-肉豆蔻酸酯乙酸盐处理171.CD4和LSTRA细胞，在体内诱导p56lck上丝氨酸-59的磷酸化，这与向p60lck的转变相关。我们还证明，相同的丝氨酸残基在体外可被丝裂原活化蛋白激酶磷酸化，并且这一事件能够在体外降低p56lck的活性。综合这些数据表明存在一种体内调节p56lck活性的新途径。
