Deckert Marcel
Inserm U576, Régulation des réponses immune et inflammatoire, Hôpital de l'Archet, Route Saint-Antoine de Ginestière, 06202 Nice, France.
Med Sci (Paris). 2006 Dec;22(12):1081-6. doi: 10.1051/medsci/200622121081.
Adaptor proteins that do not contain intrinsic enzymatic activity play a critical role in cell biology by regulating the assembly of large multimolecular signaling complexes involved in extracellular signal transduction. The increasing number of diseases associated with aberrant function or expression of adaptor proteins further illustrate their key role in cellular regulation. The adaptor 3BP2 (or SH3BP2) was originally identified more than 10 years ago as an c-Abl binding protein, and next as a partner of Syk family kinases in 1998. 3BP2 displays the typical modular organization of an adapter protein with an amino-terminal PH domain, a central proline rich region and a carboxyl-terminal SH2 domain. Although its physiological function remains unknown, studies have implicated a role for 3BP2 in immunoreceptor signaling through its interaction with a number of signaling molecules including Src and Syk families of protein tyrosine kinases, the membrane adaptor LAT, Vav exchange factors, PLC-gamma, and 14-3-3 proteins. Recently, the 3bp2/sh3bp2 locus was shown to be mutated in a rare human disease involved in cranial-facial development called cherubism, suggesting a role for 3BP2 in regulating osteoclast and hematopoietic cell function.
不含内在酶活性的衔接蛋白通过调节参与细胞外信号转导的大型多分子信号复合物的组装,在细胞生物学中发挥关键作用。与衔接蛋白功能异常或表达异常相关的疾病数量不断增加,进一步说明了它们在细胞调节中的关键作用。衔接蛋白3BP2(或SH3BP2)最初在十多年前被鉴定为一种c-Abl结合蛋白,1998年又被鉴定为Syk家族激酶的一个伙伴。3BP2具有衔接蛋白典型的模块化结构,有一个氨基末端的PH结构域、一个富含脯氨酸的中央区域和一个羧基末端的SH2结构域。尽管其生理功能尚不清楚,但研究表明3BP2通过与多种信号分子相互作用,在免疫受体信号传导中发挥作用,这些信号分子包括蛋白酪氨酸激酶的Src和Syk家族、膜衔接蛋白LAT、Vav交换因子、PLC-γ和14-3-3蛋白。最近,3bp2/sh3bp2基因座在一种罕见的涉及颅面发育的人类疾病—— cherubism中被发现发生突变,这表明3BP2在调节破骨细胞和造血细胞功能中发挥作用。