Dual regulation of SIRP α phosphorylation by integrins and CD47
Dual regulation of SIRP α phosphorylation by integrins and CD47
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DOI：
10.1074/jbc.m701565200
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发表时间：
2007-08-17
影响因子：
4.8
通讯作者：
Brown, Eric J.
中科院分区：
文献类型：
--
作者：
Johansen, Mette L.;Brown, Eric J.
信号调节蛋白α (SIRP α, SHPS- 1)是CD47的质膜受体，是吞噬、生长因子信号传导和迁移的关键调节因子。其细胞质尾部基于免疫受体酪氨酸的抑制基序的磷酸化对SIRP α的功能作用至关重要，至少在一定程度上是这样，因为磷酸化的基于免疫受体酪氨酸的抑制基序招募了Src同源2结构域的酪氨酸磷酸酶。CD47连接和整合素参与都被认为调节SIRP α磷酸化。然而，他们的独特贡献尚未得到区分。在这里，我们发现CD47的重要性因细胞类型而异，因为在髓细胞中，CD47的结扎对于SIRP α磷酸化不是必需的，而在内皮细胞中则是必需的。相反，在两种细胞类型中，整合素介导的粘附是SIRP α磷酸化所必需的。这表明SIRP α磷酸化是双重调控的，并证明了整合素和整合素相关蛋白CD47之间功能合作的新机制。
Signal regulatory protein alpha ( SIRP alpha, SHPS- 1) is a plasma membrane receptor for CD47 and a key regulator of phagocytosis, growth factor signaling, and migration. Phosphorylation of immunoreceptor tyrosine- based inhibition motifs in its cytoplasmic tail is essential for the functional effects of SIRP alpha, at least in part, because the phosphorylated immunoreceptor tyrosine-based inhibition motifs recruit Src homology 2 domain-containing tyrosine phosphatases. Ligation by CD47 and integrin engagement both have been thought to regulate SIRP alpha phosphorylation. However, their distinct contributions have not been distinguished. Here, we show that the importance of CD47 varies with cell type, since ligation of CD47 is not necessary for SIRP alpha phosphorylation in myeloid cells, whereas it is required in endothelial cells. In contrast, integrin- mediated adhesion is required for SIRP alpha phosphorylation in both cell types. This shows that SIRP alpha phosphorylation is dually regulated and demonstrates a new mechanism for functional cooperation between integrins and the integrin- associated protein CD47.