Diakonova Maria, Carter-Su Christin, Svitkina Tatyana
Biological Sciences, University of Toledo, Toledo, Ohio, USA.
University of Michigan Medical School, Ann Arbor, Michigan, USA.
MicroPubl Biol. 2025 Jan 17;2025. doi: 10.17912/micropub.biology.001451. eCollection 2025.
The widely expressed adapter protein SH2B1 was initially identified as a binding partner and substrate of tyrosine kinase JAK2. SH2B1β potentiates JAK2 activation in response to different ligands, including growth hormone, leptin and prolactin. SH2B1β has been implicated in cell motility and regulation of actin rearrangement in response to growth hormone, prolactin and platelet-derived growth factor. Here we use immunofluorescence and platinum replica electron-microscopy (PREM) technique to study localization of endogenous SH2B1. We show that endogenous SH2B localizes to two actin-rich protrusive organelles in cells: lamellipodia and filopodia. Based on this and previously published data, we suggest that at least some SH2B1 isoforms directly bind to actin filaments in both structures. Additionally, SH2B1 isoforms may work as a partner of filamin A in lamellipodia and VASP in filopodia participating in modulation of the actin cytoskeleton in response to extracellular signals.
广泛表达的衔接蛋白SH2B1最初被鉴定为酪氨酸激酶JAK2的结合伴侣和底物。SH2B1β可增强JAK2对不同配体（包括生长激素、瘦素和催乳素）的激活作用。SH2B1β与细胞运动以及在生长激素、催乳素和血小板衍生生长因子作用下的肌动蛋白重排调节有关。在此，我们使用免疫荧光和铂复型电子显微镜（PREM）技术来研究内源性SH2B1的定位。我们发现内源性SH2B定位于细胞中两种富含肌动蛋白的突出细胞器：片状伪足和丝状伪足。基于此以及先前发表的数据，我们认为至少某些SH2B1亚型在这两种结构中均直接与肌动蛋白丝结合。此外，SH2B1亚型可能在片状伪足中作为细丝蛋白A的伴侣，在丝状伪足中作为vasodilator-stimulated phosphoprotein（VASP）的伴侣，参与响应细胞外信号对肌动蛋白细胞骨架的调节。
