Veillette A, Fournel M
McGill Cancer Centre, McGill University, Montreal, Canada.
Oncogene. 1990 Oct;5(10):1455-62.
Antibody-mediated aggregation of the CD4 T-cell surface antigen activates bound p56lck molecules and can result in increased intracellular tyrosine protein phosphorylation. To evaluate the basis of the CD4 induced tyrosine phosphorylation signal, we have studied the ability of CD4 to regulate the function of p56lck when these two molecules are co-expressed in non-lymphoid cells. Our studies indicate that cross-linking of CD4 is capable of activation of p56lck in fibroblasts in a manner analogous to that previously reported for T-lymphocytes. They also demonstrate that replacement of the major site of autophosphorylation of p56lck (tyrosine 394) by a phenylalanine residue abolishes the ability to activate p56lck by CD4 cross-linking, implying that this residue is critical for the positive regulation of the Lck tyrosine kinase activity by CD4. Contrary to what we have previously reported for an antigen-dependent murine T-cell clone, as well as murine thymocytes, the CD4 induced activation of p56lck observed in fibroblasts does not result in marked changes in Lck tyrosine phosphorylation, suggesting that other lymphoid specific components may be required for these tyrosine phosphorylation changes.
抗体介导的CD4 T细胞表面抗原聚集激活结合的p56lck分子，并可导致细胞内酪氨酸蛋白磷酸化增加。为了评估CD4诱导的酪氨酸磷酸化信号的基础，我们研究了在非淋巴细胞中共表达这两种分子时CD4调节p56lck功能的能力。我们的研究表明，CD4的交联能够以类似于先前报道的T淋巴细胞的方式激活成纤维细胞中的p56lck。研究还表明，用苯丙氨酸残基取代p56lck的主要自磷酸化位点（酪氨酸394）可消除CD4交联激活p56lck的能力，这意味着该残基对于CD4对Lck酪氨酸激酶活性的正向调节至关重要。与我们之前报道的抗原依赖性小鼠T细胞克隆以及小鼠胸腺细胞相反，在成纤维细胞中观察到的CD4诱导的p56lck激活并未导致Lck酪氨酸磷酸化的明显变化，这表明这些酪氨酸磷酸化变化可能需要其他淋巴样特异性成分。
