在 EGF 刺激的细胞中，SPE-39 通过酪氨酸磷酸化和泛素化抑制 Vps33B 的功能。

Inhibitory effect of SPE-39 due to tyrosine phosphorylation and ubiquitination on the function of Vps33B in the EGF-stimulated cells.

机构信息

Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Hiroshima 727-0023, Japan.

出版信息

FEBS Lett. 2012 Jul 30;586(16):2245-50. doi: 10.1016/j.febslet.2012.05.051. Epub 2012 Jun 4.

DOI:10.1016/j.febslet.2012.05.051

Abstract

Although SPE-39 is a binding protein to Vps33B that is one of the subunit in the mammalian HOPS complex, the elements of SPE-39 function remain unknown. Here, we show that tyrosine phosphorylation of SPE-39 following EGF stimulation plays a role in the stability of SPE-39 itself. Ubiquitination of the C-terminal region of SPE-39 was also elevated in response to EGF stimulation, and this process was regulated by the phosphorylation of Tyr-11 in SPE-39. However, association of Vps33B with SPE-39 inhibited the elevation of ubiquitination of SPE-39 following EGF stimulation, which might be responsible for the stabilization of SPE-39. Furthermore, an opposing functional relationship between SPE-39 and Vps33B on the downregulation of the EGF receptor was observed in EGF-stimulated COS-7 cells.

摘要

虽然 SPE-39 是与 Vps33B 结合的蛋白质，Vps33B 是哺乳动物 HOPS 复合物的一个亚基，但 SPE-39 的功能元件仍不清楚。在这里，我们表明 EGF 刺激后 SPE-39 的酪氨酸磷酸化在 SPE-39 自身稳定性中起作用。SPE-39 的 C 末端区域的泛素化也响应 EGF 刺激而升高，并且该过程受 SPE-39 中 Tyr-11 的磷酸化调节。然而，Vps33B 与 SPE-39 的结合抑制了 EGF 刺激后 SPE-39 泛素化的升高，这可能是 SPE-39 稳定的原因。此外，在 EGF 刺激的 COS-7 细胞中观察到 SPE-39 和 Vps33B 之间在 EGF 受体下调方面的功能关系相反。