Timson Gauen L K, Kong A N, Samelson L E, Shaw A S
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Mol Cell Biol. 1992 Dec;12(12):5438-46. doi: 10.1128/mcb.12.12.5438-5446.1992.
Several lines of evidence link the protein tyrosine kinase p59fyn to the T-cell receptor. The molecular basis of this interaction has not been established. Here we show that the tyrosine kinase p59fyn can associate with chimeric proteins that contain the cytoplasmic domains of CD3 epsilon, gamma, zeta (zeta), and eta. Mutational analysis of the zeta cytoplasmic domain demonstrated that the membrane-proximal 41 residues of zeta are sufficient for p59fyn binding and that at least two p59fyn binding domains are present. The association of p59fyn with the zeta chain was specific, as two closely related Src family protein tyrosine kinases, p60src and p56lck, did not associate with a chimeric protein that contained the cytoplasmic domain of zeta. Mutational analysis of p59fyn revealed that a 10-amino-acid sequence in the unique amino-terminal domain of p59fyn was responsible for the association with zeta. These findings support evidence that p59fyn is functionally and structurally linked to the T-cell receptor. More importantly, these studies support a critical role for the unique amino-terminal domains of Src family kinases in the coupling of tyrosine kinases to the signalling pathways of cell surface receptors.
多条证据表明蛋白酪氨酸激酶p59fyn与T细胞受体相关。这种相互作用的分子基础尚未明确。在此我们表明，酪氨酸激酶p59fyn能够与包含CD3ε、γ、ζ（ζ）和η胞质结构域的嵌合蛋白结合。对ζ胞质结构域的突变分析表明，ζ靠近膜的41个残基足以与p59fyn结合，并且至少存在两个p59fyn结合结构域。p59fyn与ζ链的结合具有特异性，因为两个密切相关的Src家族蛋白酪氨酸激酶p60src和p56lck不与包含ζ胞质结构域的嵌合蛋白结合。对p59fyn的突变分析表明，p59fyn独特的氨基末端结构域中的一个10个氨基酸的序列负责与ζ结合。这些发现支持了p59fyn在功能和结构上与T细胞受体相关的证据。更重要的是，这些研究支持Src家族激酶独特的氨基末端结构域在将酪氨酸激酶与细胞表面受体的信号通路偶联中起关键作用。
