Lago Paz F, Galgani M, D'Oro U, Matarese G, Masci A M, Zappacosta S, Racioppi L
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Naples, Italy.
Eur J Immunol. 2001 Mar;31(3):777-82. doi: 10.1002/1521-4141(200103)31:3<777::aid-immu777>3.0.co;2-i.
CD45 is a widely distributed phosphatase which modulates the activity of Lck by controlling the phosphorylation status of two tyrosine residues localized in the catalytic activation loop and in the negative regulatory domain. Little is known about the regulation of CD45 activity upon T cell activation. In the present study, we found that, in resting lymphocytes, an enzymatically active fraction of CD45 molecules is associated to the CD4 coreceptor. TCR engagement by an agonist ligand markedly inhibited this pool of CD45 phosphatase without affecting the CD4 / CD45 association. These results reveal that the modulation of the CD4-associated CD45 phosphatase activity is a very early biochemical event triggered by TCR stimulation. Since the recruitment of CD4 is an initial step in the activation process, the inhibition of this pool of CD45 molecules would be crucial to prevent dephosphorylation of relevant substrates which promote the activation process.
CD45是一种广泛分布的磷酸酶，它通过控制位于催化激活环和负调控域的两个酪氨酸残基的磷酸化状态来调节Lck的活性。关于T细胞激活后CD45活性的调节知之甚少。在本研究中，我们发现，在静息淋巴细胞中，一部分具有酶活性的CD45分子与CD4共受体相关联。激动剂配体与TCR结合显著抑制了这部分CD45磷酸酶，而不影响CD4/CD45的结合。这些结果表明，CD4相关的CD45磷酸酶活性的调节是TCR刺激引发的一个非常早期的生化事件。由于CD4的募集是激活过程的第一步，抑制这部分CD45分子对于防止促进激活过程的相关底物去磷酸化至关重要。
