IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3 binds SHC1

Inferred from mouse: Coimmunoprecipitation studies show that SHC transforming protein 1 (SHC1) associates with Interleukin-2 receptor subunit beta (IL2RB, IL2Rβ) as part of the Interleukin-2 (IL2) receptor complex (Gadina et al. 2000). Similar binding in IL15 receptor complex can be inferred from IL15 stimulates SHC1 phosphorylation (Zambricki et al. 2005). More in detail, human and mouse IL15 have 70.2% amino acid sequence similarity and exhibit similar trans-presentation mechanism, signal transduction machinery and biological activities. Similarly, human IL15 shows cross-reactivity with mouse cells and it was demonstrated that human and mouse IL15 showed similar responses in mouse models (Stoklasek et al. 2006) (Patidar et al. data not published). IL15 helps in B cell proliferation via two pathways: IL15–STAT5 and IL15–SHC–Ras–Raf–ERK pathway (Patidar et al. 2016).This is a black box event because there is no direct evidence of SHC1 binding after IL15 stimulation.

根据小鼠研究推断，共免疫沉淀研究表明SHC转化蛋白1（SHC1）作为IL-2受体复合体（Gadina等，2000年）的一部分，与IL-2受体亚基β（IL2RB，IL2Rβ）相结合。从IL15受体复合体的类似结合中可以推断出，IL15刺激SHC1磷酸化（Zambricki等，2005年）。更详细地说，人源和鼠源IL15在氨基酸序列上具有70.2%的相似性，并展现出相似的跨膜传递机制、信号转导机制以及生物学活性。类似地，人源IL15与小鼠细胞表现出交叉反应性，且已有研究表明，人源和鼠源IL15在鼠模型中表现出相似的反应（Stoklasek等，2006年）（Patidar等，数据未发表）。IL15通过两条途径促进B细胞增殖：IL15-STAT5途径和IL15-SHC-Ras-Raf-ERK途径（Patidar等，2016年）。这是一个黑盒事件，因为在IL15刺激后没有直接证据表明SHC1的结合。