Hermiston Michelle L, Zikherman Julie, Zhu Jing W
Department of Pediatrics, University of California, San Francisco, CA 94143, USA.
Immunol Rev. 2009 Mar;228(1):288-311. doi: 10.1111/j.1600-065X.2008.00752.x.
Reciprocal regulation of tyrosine phosphorylation by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) is central to normal immune cell function. Disruption of the equilibrium between PTK and PTP activity can result in immunodeficiency, autoimmunity, or malignancy. Src family kinases (SFKs) 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 SFKs activity is critical for appropriate responses to stimulation of these various signaling pathways, it is perhaps not surprising that multiple PTPs are involved in their regulation. Here, we focus on the role of three phosphatases, CD45, CD148, and LYP/PEP, which are critical regulators of SFKs 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.
蛋白酪氨酸激酶（PTK）和蛋白酪氨酸磷酸酶（PTP）对酪氨酸磷酸化的相互调节是正常免疫细胞功能的核心。PTK和PTP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（SFK）在免疫细胞功能和疾病中均发挥核心作用，因为它们在众多信号转导级联反应中处于近端位置，这些级联反应包括源自整合素、T细胞和B细胞抗原受体、Fc、生长因子和细胞因子受体的反应。鉴于严格调控SFK活性对于对这些各种信号通路刺激的适当反应至关重要，多个PTP参与其调控或许并不令人惊讶。在此，我们重点关注三种磷酸酶CD45、CD148和LYP/PEP的作用，它们是造血细胞中SFK的关键调节因子。我们综述了目前对它们的结构、表达、在不同造血细胞亚群中的功能、调控以及在疾病中的假定作用的理解。最后，我们讨论了如果我们要更清楚地了解造血细胞中酪氨酸磷酸化和信号网络的协调调控以及它们在疾病中如何可能被治疗性操控，仍需解决的问题。
