Matuoka K, Miki H, Takahashi K, Takenawa T
Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Japan.
Biochem Biophys Res Commun. 1997 Oct 20;239(2):488-92. doi: 10.1006/bbrc.1997.7492.
Nck is a small protein composed of Src homology regions (SH) 2 and 3, paralleling the adaptors c-Crk and Grb2/Ash, but its function remains enigmatic. To clarify Nck signaling, a human brain cDNA library was searched for targets of the SH3 moiety of Nck. A novel molecule detected therefrom (referred to as Nck-, Ash- and phospholipase Cgamma-binding protein 4) contained proline-rich sequences and, through the function of one of them, interacted with the middle SH3 domain of Nck. A NAP4 fusion peptide exhibited an affinity for Nck, Ash and phospholipase Cgamma in whole cell lysates. NAP4 also had an SH2 domain, which could bind to activated EGF receptor. These intermolecular interactions imply the intricacy of Nck-mediated signaling around the receptor protein-tyrosine kinases. In addition, NAP4 bore a putative nuclear localization signal and a Q-run/P-run composite, both characteristic of nuclear proteins, and might therefore relate to the presence of Nck in the cellular nucleus.
Nck是一种由Src同源区（SH）2和3组成的小蛋白，与衔接蛋白c-Crk和Grb2/Ash相似，但其功能仍不清楚。为了阐明Nck信号传导，我们在人脑海马cDNA文库中寻找Nck的SH3部分的靶点。从中检测到的一种新分子（称为Nck、Ash和磷脂酶Cγ结合蛋白4）含有富含脯氨酸的序列，并通过其中一个序列的功能与Nck的中间SH3结构域相互作用。NAP4融合肽在全细胞裂解物中对Nck、Ash和磷脂酶Cγ表现出亲和力。NAP4还具有一个SH2结构域，可与活化的表皮生长因子受体结合。这些分子间相互作用暗示了受体蛋白酪氨酸激酶周围Nck介导信号传导的复杂性。此外，NAP4带有一个假定的核定位信号和一个Q链/P链复合物，这两者都是核蛋白的特征，因此可能与Nck在细胞核中的存在有关。
