Palmitoylation‐dependent endosomal localization of AATYK1A and its interaction with Src
Palmitoylation‐dependent endosomal localization of AATYK1A and its interaction with Src
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DOI：
10.1111/j.1365-2443.2008.01219.x
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发表时间：
2008-09
期刊：
影响因子：
2.1
通讯作者：
Koji Tsutsumi;M. Tomomura;T. Furuichi;S. Hisanaga
中科院分区：
文献类型：
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作者：
Koji Tsutsumi;M. Tomomura;T. Furuichi;S. Hisanaga
凋亡相关酪氨酸激酶1 (AATYK1)，也被称为LMTK1，先前从32Dcl3髓系前体细胞中分离出凋亡相关基因，但其确切功能尚不清楚。AATYK1A是一种无跨膜结构域的异构体，在神经元中高度表达。我们在皮质培养的神经元和COS - 7细胞中发现了AATYK1A在三个N端半胱氨酸残基上的棕榈酰化，并发现棕榈酰化决定了AATYK1A在转铁蛋白受体阳性循环内体上的定位。此外，我们发现酪氨酸激酶Src是一种新的AATYK1A相互作用蛋白。Src和Fyn以棕榈酰化依赖的方式磷酸化AATYK1A的酪氨酸25和46。AATYK1A与Src在核内体中的关联也被发现依赖于棕榈酰化。这些结果表明，棕榈酰化不仅是AATYK1A亚细胞定位的关键因素，也是其与Src相互作用的关键因素。
Apoptosis‐associated tyrosine kinase 1 (AATYK1), also named LMTK1, was previously isolated as an apoptosis‐related gene from 32Dcl3 myeloid precursor cells, but its precise function remains unknown. AATYK1A, an isoform without a transmembrane domain, is highly expressed in neurons. We identified palmitoylation of AATYK1A at three N‐terminal cysteine residues in cortical cultured neurons and COS‐7 cells and found that palmitoylation determined localization of AATYK1A to the transferrin receptor‐positive recycling endosomes. Further, we identified the tyrosine kinase Src as a novel AATYK1A‐interacting protein. Src and Fyn phosphorylated AATYK1A at tyrosines 25 and 46 in a palmitoylation‐dependent manner. The association of AATYK1A with Src in endosomes was also found to be palmitoylation‐dependent. These results indicate that palmitoylation is a critical factor not only for the subcellular localization of AATYK1A but also for its interaction with Src.