Braun L, Ghebrehiwet B, Cossart P
Unité des Interactions Bactéries-Cellules, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France.
EMBO J. 2000 Apr 3;19(7):1458-66. doi: 10.1093/emboj/19.7.1458.
InlB is a Listeria monocytogenes protein that promotes entry of the bacterium into mammalian cells by stimulating tyrosine phosphorylation of the adaptor proteins Gab1, Cbl and Shc, and activation of phosphatidyl- inositol (PI) 3-kinase. Using affinity chromatography and enzyme-linked immunosorbent assay, we demonstrate a direct interaction between InlB and the mammalian protein gC1q-R, the receptor of the globular part of the complement component C1q. Soluble C1q or anti-gC1q-R antibodies impair InlB-mediated entry. Transient transfection of GPC16 cells, which are non-permissive to InlB-mediated entry, with a plasmid-expressing human gC1q-R promotes entry of InlB-coated beads. Furthermore, several experiments indicate that membrane recruitment and activation of PI 3-kinase involve an InlB-gC1q-R interaction and that gC1q-R associates with Gab1 upon stimulation of Vero cells with InlB. Thus, gC1q-R constitutes a cellular receptor involved in InlB-mediated activation of PI 3-kinase and tyrosine phosphorylation of the adaptor protein Gab1. After E-cadherin, the receptor for internalin, gC1q-R is the second identified mammalian receptor promoting entry of L. monocytogenes into mammalian cells.
内化素B(InlB)是一种单核细胞增生李斯特菌蛋白,它通过刺激衔接蛋白Gab1、Cbl和Shc的酪氨酸磷酸化以及磷脂酰肌醇(PI)3激酶的激活,促进该细菌进入哺乳动物细胞。利用亲和层析和酶联免疫吸附测定,我们证明了InlB与哺乳动物蛋白gC1q-R(补体成分C1q球状部分的受体)之间存在直接相互作用。可溶性C1q或抗gC1q-R抗体可损害InlB介导的进入过程。用表达人gC1q-R的质粒瞬时转染对InlB介导的进入不敏感的GPC16细胞,可促进包被InlB的珠子进入细胞。此外,多项实验表明,PI 3激酶的膜募集和激活涉及InlB与gC1q-R的相互作用,并且在用InlB刺激Vero细胞后,gC1q-R与Gab1结合。因此,gC1q-R构成了一种细胞受体,参与InlB介导的PI 3激酶激活以及衔接蛋白Gab1的酪氨酸磷酸化。继内化素的受体E-钙黏蛋白之后,gC1q-R是第二种被鉴定出的促进单核细胞增生李斯特菌进入哺乳动物细胞的哺乳动物受体。