Role of SHIP1 in cancer and mucosal inflammation.
Role of SHIP1 in cancer and mucosal inflammation.
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DOI：
10.1111/nyas.12038
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发表时间：
2013-03
影响因子：
5.2
通讯作者：
Kerr WG
中科院分区：
文献类型：
--
作者：
Fernandes S;Iyer S;Kerr WG
含SH-2的肌醇5'多磷酸酶1（SHIP 1）是主要由造血细胞表达的多功能蛋白。SHIP 1从PI 3 K产物PI（3，4，5）P3中除去5'磷酸，以产生PI（3，4）P2。两种PIP物质都影响Akt的活性水平，并最终调节细胞的存活和分化。SHIP 1还具有几个蛋白质相互作用结构域，赋予其许多非酶细胞信号传导或受体掩蔽功能。在这篇综述中，我们讨论了SHIP 1在癌症和粘膜炎症中的相反作用。一方面，SHIP 1的生殖系缺失导致骨髓性肺实变和回肠中的严重炎症，这是一种非常类似于人克罗恩病的表型，并且可以通过用SHIP 1感受态T细胞重建来挽救。另一方面，瞬时抑制癌细胞中SHIP 1的酶活性导致细胞凋亡并提高致死性小鼠异种移植模型中的存活率。总体而言，仔细解剖几种疾病中涉及的不同病理机制为靶向SHIP 1的治疗干预提供了新的机会。
The SH-2 containing inositol 5’ polyphosphatase 1 (SHIP1) is a multifunctional protein expressed predominantly, by hematopoietic cells. SHIP1 removes the 5’ phosphate from the product of PI3K, PI(3,4,5)P3, to generate PI(3,4)P2. Both PIP species influence the activity level of Akt, and ultimately regulate cell survival and differentiation. SHIP1 also harbors several protein interaction domains that endow it with many non-enzymatic cell signaling or receptor masking functions. In this review, we discuss the opposing roles of SHIP1 in cancer and in mucosal inflammation. On one hand, germline loss of SHIP1 causes myeloid lung consolidation and severe inflammation in the ileum, a phenotype that closely mimics human Crohn’s Disease and can be rescued by reconstitution with SHIP1 competent T cells. On the other, transient inhibition of the enzymatic activity of SHIP1 in cancer cell leads to apoptosis and enhances survival in lethal murine xenograft models. Overall, careful dissection of the different pathological mechanisms involved in several diseases provides novel opportunities for therapeutic intervention targeting SHIP1.
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影响因子：
20.3
作者：
Hazen, Amy L.;Smith, Michelle J.;Kerr, William G.
通讯作者：
Kerr, William G.
影响因子：
10.5
作者：
Liu, QR;Sasaki, T;Penninger, JM
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Penninger, JM
影响因子：
4.4
作者：
Brooks, Robert;Fuhler, Gwenny M.;Kerr, William G.
通讯作者：
Kerr, William G.
影响因子：
20.3
作者：
Ong, Christopher J.;Ming-Lum, Andrew;Mui, Alice L. -F.
通讯作者：
Mui, Alice L. -F.
影响因子：
56.9
作者：
Wang, JW;Howson, JM;Kerr, WG
通讯作者：
Kerr, WG