Okada H, Bolland S, Hashimoto A, Kurosaki M, Kabuyama Y, Iino M, Ravetch J V, Kurosaki T
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan.
J Immunol. 1998 Nov 15;161(10):5129-32.
Src homology-2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP) is a recently identified protein that has been implicated as an important signaling molecule. Although SHIP has been shown to participate in the FcgammaRIIB-mediated inhibitory signal, the functional role of SHIP in activation responses by immunoreceptor tyrosine-based activation motif-bearing receptors such as B cell receptor (BCR) remains unclear. Indeed, it has been proposed that SHIP serves as a linking molecule for the regulation of the extracellular signal-regulated kinase pathway in BCR signaling, because SHIP associates with Shc. We now report that SHIP-deficient DT40 B cells display enhanced Ca2+ mobilization in response to BCR ligation, whereas extracellular signal-regulated kinase activation is unaffected. This Ca2+ enhancement is due to a sustained intracellular Ca2+ increase or to long-lasting Ca2+ oscillations by loss of SHIP, as revealed by single-cell Ca2+ imaging analysis. These results demonstrate the importance of SHIP in B cell activation by the modulation of Ca2+ mobilization.
含Src同源2结构域的肌醇多磷酸5'-磷酸酶（SHIP）是最近发现的一种蛋白质，被认为是一种重要的信号分子。尽管SHIP已被证明参与FcγRIIB介导的抑制性信号，但SHIP在基于免疫受体酪氨酸的激活基序的受体（如B细胞受体（BCR））激活反应中的功能作用仍不清楚。事实上，有人提出SHIP作为一种连接分子，用于调节BCR信号传导中的细胞外信号调节激酶途径，因为SHIP与Shc相关联。我们现在报告，SHIP缺陷的DT40 B细胞在响应BCR连接时显示出增强的Ca2+动员，而细胞外信号调节激酶激活不受影响。单细胞Ca2+成像分析表明，这种Ca2+增强是由于SHIP缺失导致细胞内Ca2+持续增加或长期Ca2+振荡。这些结果证明了SHIP通过调节Ca2+动员在B细胞激活中的重要性。
