CD45, CD148, and Lyp/Pep: critical phosphatases regulating Src family kinase signaling networks in immune cells.
CD45, CD148, and Lyp/Pep: critical phosphatases regulating Src family kinase signaling networks in immune cells.
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DOI：
10.1111/j.1600-065x.2008.00752.x
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发表时间：
2009-03
影响因子：
8.7
通讯作者：
Zhu JW
中科院分区：
文献类型：
--
作者：
Hermiston ML;Zikherman J;Zhu JW
蛋白酪氨酸激酶和磷酸酶对酪氨酸磷酸化的相互调节是正常免疫细胞功能的核心。蛋白酪氨酸激酶和磷酸酶活性之间平衡的破坏可导致免疫缺陷、自身免疫或恶性肿瘤。Src家族激酶在免疫细胞功能和疾病中起中心作用，这是由于它们在许多信号转导级联中的近端位置，包括源自整联蛋白、T和B细胞抗原受体、Fc、生长因子和细胞因子受体的那些。考虑到Src家族激酶活性的严格调节对于对这些各种信号传导途径的刺激的适当响应是至关重要的，因此多种蛋白酪氨酸磷酸酶参与其调节可能并不奇怪。在这里，我们专注于三个磷酸酶，CD 45，CD 148和LYP/PEP，这是造血细胞中src家族激酶活性的关键调节剂的作用。我们回顾我们目前的理解，他们的结构，表达，在不同的造血细胞亚群，调节功能，并假定在疾病中的作用。最后，我们讨论了剩余的问题，必须解决，如果我们要有一个更清楚的了解协调调节的酪氨酸磷酸化和造血细胞中的信号网络，以及它们如何可能被操纵治疗疾病。
Reciprocal regulation of tyrosine phosphorylation by protein tyrosine kinases and phosphatases is central to normal immune cell function. Disruption of the equilibrium between protein tyrosine kinase and phosphatase activity can result in immunodeficiency, autoimmunity, or malignancy. Src family kinases play a central role in both immune cell function and disease due to their proximal position in numerous signal transduction cascades including those emanating from integrin, T and B cell antigen receptors, Fc, growth factor, and cytokine receptors. Given that tight regulation of Src family kinase activity is critical for appropriate responses to stimulation of these various signaling pathways, it is perhaps not surprising that multiple protein tyrosine phosphatases are involved in their regulation. Here, we focus on the role of three phosphatases, CD45, CD148, and LYP/PEP, which are critical regulators of src family kinase activity in hematopoietic cells. We review our current understanding of their structures, expression, functions in different hematopoietic cell subsets, regulation, and putative roles in disease. Finally, we discuss remaining questions that must be addressed if we are to have a clearer understanding of the coordinated regulation of tyrosine phosphorylation and signaling networks in hematopoietic cells and how they could potentially be manipulated therapeutically in disease.