A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP
A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP
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DOI：
10.1074/jbc.m007251200
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发表时间：
2000-12-01
影响因子：
4.8
通讯作者：
Kitamura, N
中科院分区：
文献类型：
--
作者：
Kato, M;Miyazawa, K;Kitamura, N
Hrs结合蛋白（Hbp）是一种含有Src同源3（SH 3）结构域的蛋白质，与Hrs紧密结合。Hbp与Hrs一起被认为在生长因子-受体复合物通过早期内体的内吞运输中起调节作用。Hbp通过SH 3结构域与结合配偶体的结合似乎是Hbp发挥其功能所必需的。在本研究中，我们通过远Western筛选来寻找Hbp结合蛋白，并分离了编码去泛素化酶mUBPY的小鼠cDNA克隆作为Hbp SH 3结合蛋白，mUBPY具有两个Hbp-SH 3结构域结合位点。突变分析鉴定了共有序列PX（V/I）（D/N）RXXKP作为Hbp-SH 3结构域结合基序。它是一种新的SH 3结合基序，不含经典的富含脯氨酸的共有结合基序PXXP。生长因子受体的泛素化被认为调节其细胞内降解。因此，UBPY可能通过新的SH 3结合基序与Hbp的SH 3结构域相互作用而在降解中发挥调节作用。
Hrs-binding protein (Hbp) is a Src homology 3 (SH3) domain-containing protein that tightly associates with Hrs. Hbp together with Hrs is thought to play a regulatory role in endocytic trafficking of growth factor-receptor complexes through early endosomes. Association of Hbp with a binding partner(s) via the SH3 domain seems to be essential for Hbp to exert its function. In this study, we searched for Hbp-binding proteins by a far Western screening and isolated a mouse cDNA clone encoding a deubiquitinating enzyme mUBPY as an Hbp SH3-binding protein, mUBPY has two Hbp-SH3 domain binding sites. Mutagenic analysis identified a consensus sequence PX(V/I)(D/N)RXXKP as the Hbp-SH3 domain binding motif. It is a novel SH3-binding motif and does not contain the canonical proline-rich consensus binding motif, PXXP. Ubiquitination of growth factor receptors is thought to regulate their intracellular degradation. Thus, UBPY may play a regulatory role in the degradation by interaction with the SH3 domain of Hbp via the novel SH3-binding motif.