Department of Clinical Medicine and Surgery, University of Naples Federico II, School of Medicine, Via S. Pansini 5, 80131 Naples, Italy.
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, School of Medicine, Via S. Pansini 5, 80131 Naples, Italy.
Int J Mol Sci. 2020 May 27;21(11):3818. doi: 10.3390/ijms21113818.
FPR1, FPR2, and FPR3 are members of Formyl Peptides Receptors (FPRs) family belonging to the GPCR superfamily. FPR2 is a low affinity receptor for formyl peptides and it is considered the most promiscuous member of this family. Intracellular signaling cascades triggered by FPRs include the activation of different protein kinases and phosphatase, as well as tyrosine kinase receptors transactivation. Protein kinases and phosphatases act coordinately and any impairment of their activation or regulation represents one of the most common causes of several human diseases. Several phospho-sites has been identified in protein kinases and phosphatases, whose role may be to expand the repertoire of molecular mechanisms of regulation or may be necessary for fine-tuning of switch properties. We previously performed a phospho-proteomic analysis in FPR2-stimulated cells that revealed, among other things, not yet identified phospho-sites on six protein kinases and one protein phosphatase. Herein, we discuss on the selective phosphorylation of Serine/Threonine-protein kinase N2, Serine/Threonine-protein kinase PRP4 homolog, Serine/Threonine-protein kinase MARK2, Serine/Threonine-protein kinase PAK4, Serine/Threonine-protein kinase 10, Dual specificity mitogen-activated protein kinase kinase 2, and Protein phosphatase 1 regulatory subunit 14A, triggered by FPR2 stimulation. We also describe the putative FPR2-dependent signaling cascades upstream to these specific phospho-sites.
FPR1、FPR2 和 FPR3 是属于 G 蛋白偶联受体超家族的 Formyl Peptides Receptors (FPRs) 家族的成员。FPR2 是一种低亲和力的 Formyl Peptides 受体，被认为是该家族中最混杂的成员。FPRs 触发的细胞内信号级联包括不同蛋白激酶和磷酸酶的激活，以及酪氨酸激酶受体的反式激活。蛋白激酶和磷酸酶协同作用，其激活或调节的任何损害都是许多人类疾病的最常见原因之一。在蛋白激酶和磷酸酶中已经鉴定出几个磷酸化位点，其作用可能是扩展调节的分子机制谱，或者可能是精细调节开关特性所必需的。我们之前在 FPR2 刺激的细胞中进行了磷酸蛋白质组学分析，除其他外，还揭示了六种蛋白激酶和一种蛋白磷酸酶上尚未确定的磷酸化位点。在此，我们讨论了 FPR2 刺激引发的丝氨酸/苏氨酸蛋白激酶 N2、丝氨酸/苏氨酸蛋白激酶 PRP4 同源物、丝氨酸/苏氨酸蛋白激酶 MARK2、丝氨酸/苏氨酸蛋白激酶 PAK4、丝氨酸/苏氨酸蛋白激酶 10、双特异性有丝分裂原激活蛋白激酶激酶 2 和蛋白磷酸酶 1 调节亚基 14A 的选择性磷酸化。我们还描述了这些特定磷酸化位点上游的推定 FPR2 依赖性信号级联。
