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首页> 外文期刊>Molecular and Cellular Biology >Identification of a Novel Family of Targets of PYK2 Related to Drosophila Retinal Degeneration B (rdgB) Protein
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Identification of a Novel Family of Targets of PYK2 Related to Drosophila Retinal Degeneration B (rdgB) Protein

机译：与果蝇视网膜变性B（rdgB）蛋白相关的新型PYK2靶标家族的鉴定

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The protein tyrosine kinase PYK2 has been implicated in signaling pathways activated by G-protein-coupled receptors, intracellular calcium, and stress signals. Here we describe the molecular cloning and characterization of a novel family of PYK2-binding proteins designated Nirs (PYK2 N-terminal domain-interacting receptors). The three Nir proteins (Nir1, Nir2, and Nir3) bind to the amino-terminal domain of PYK2 via a conserved sequence motif located in the carboxy terminus. The primary structures of Nirs reveal six putative transmembrane domains, a region homologous to phosphatidylinositol (PI) transfer protein, and an acidic domain. The Nir proteins are the human homologues of the Drosophila retinal degeneration B protein (rdgB), a protein implicated in the visual transduction pathway in flies. We demonstrate that Nirs are calcium-binding proteins that exhibit PI transfer activity in vivo. Activation of PYK2 by agents that elevate intracellular calcium or by phorbol ester induce tyrosine phosphorylation of Nirs. Moreover, PYK2 and Nirs exhibit similar expression patterns in several regions of the brain and retina. In addition, PYK2-Nir complexes are detected in lysates prepared from cultured cells or from brain tissues. Finally, the Nir1-encoding gene is located at human chromosome 17p13.1, in proximity to a locus responsible for several human retinal diseases. We propose that the Nir and rdgB proteins represent a new family of evolutionarily conserved PYK2-binding proteins that play a role in the control of calcium and phosphoinositide metabolism downstream of G-protein-coupled receptors.
机译：酪氨酸蛋白激酶PYK2已参与G蛋白偶联受体，细胞内钙和应激信号激活的信号通路。在这里，我们描述了命名为Nirs（PYK2 N末端域相互作用受体）的PYK2结合蛋白新家族的分子克隆和特征。三个Nir蛋白（Nir1，Nir2和Nir3）通过位于羧基末端的保守序列基序与PYK2的氨基末端结构域结合。 Nirs的一级结构揭示了六个推定的跨膜结构域，一个与磷脂酰肌醇（PI）转移蛋白同源的区域和一个酸性结构域。 Nir蛋白是果蝇视网膜变性B蛋白（rdgB）的人类同源物，该蛋白与果蝇的视觉转导途径有关。我们证明尼尔斯是钙结合蛋白，在体内表现出PI转移活性。通过升高细胞内钙的试剂或佛波醇酯对PYK2的激活会诱导Nirs的酪氨酸磷酸化。此外，PYK2和Nirs在大脑和视网膜的多个区域表现出相似的表达模式。另外，在从培养细胞或脑组织制备的裂解物中检测到PYK2-Nir复合物。最后，编码Nir1的基因位于人类染色体17p13.1，靠近负责几种人类视网膜疾病的基因座。我们建议，Nir和rdgB蛋白代表了一个新的进化保守PYK2结合蛋白家族，它们在G蛋白偶联受体下游控制钙和磷酸肌醇代谢中发挥作用。

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