Internalisation of the insulin receptor

Almost concomitantly a second effect resulting from the tyrosine phosphorylation of the insulin receptor begins to occur. The phosphorylation of the tyrosine in the NPEY sequence found in the juxtamembrane is also a signal for endocytosis to occur. Whilst invagination of the plasma membrane commences the receptor tyrosine kinase activity continues unabated as does substrate phosphorylation.<p>As the invagination continues certain proteins are concentrated in the area of invagination. In addition to the insulin receptor itself there is a recruitment of insulin-specific protein tyrosine phosphatases (PTPs). This process takes less than one minute. (The identity of these PTPs is not clearly established yet.)<p>The formation of the endosome containing the activated ligand-receptor complex is completed within two minutes following ligand presentation at the plasma membrane and is maximal by five minutes. Endocytosis of activated receptors has the dual effect of concentrating receptors within endosomes and allowing the insulin receptor tyrosine kinase to phosphorylate substrates that are spatially distinct from those accessible at the plasma membrane. The endosome also contains other proteins crucial to the signal transduction process. These include a proton pump and the insulin degrading activity. It is not certain how these proteins arrive in the endosome since it could be via the endosome maturation or fusion pathways.

几乎同时，由胰岛素受体的酪氨酸磷酸化引起的第二种效应开始显现。存在于细胞膜内侧的NPEY序列中酪氨酸的磷酸化，也是启动内吞作用的一个信号。随着细胞膜内陷的开始，受体酪氨酸激酶活性持续未受干扰，底物磷酸化亦然。随着内陷的继续，某些蛋白质在凹陷区域浓缩。除了胰岛素受体本身，还有胰岛素特异性蛋白酪氨酸磷酸酶（PTPs）的募集。这一过程不到一分钟即可完成。（这些PTPs的身份尚未明确确定。）在细胞膜上呈递配体后两分钟内，包含激活的配体-受体复合物的内体形成完成，并在五分钟时达到最大。激活受体的内吞作用具有双重效果，即在内体中浓缩受体，并允许胰岛素受体酪氨酸激酶磷酸化那些在空间上与细胞膜可接触的底物相异化的底物。内体还含有对信号转导过程至关重要的其他蛋白质，包括质子泵和胰岛素降解活性。由于这些蛋白质可能通过内体成熟或融合途径进入内体，因此其进入内体的确切方式尚不明确。