Protein expression levels of the Src activating protein AFAP are developmentally regulated in brain
Protein expression levels of the Src activating protein AFAP are developmentally regulated in brain
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DOI：
10.1002/neu.10143
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发表时间：
2003-02-15
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影响因子：
--
通讯作者：
Flynn, DC
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文献类型：
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作者：
Clump, DA;Clem, R;Flynn, DC
非受体酪氨酸激酶Src家族在调节影响生长锥延伸、神经元分化和脑发育的信号中起重要作用。最近的报道表明，Src SH 2/SH 3结合伴侣AFAP-110具有作为cSrc活化蛋白和作为肌动蛋白丝捆绑蛋白调节肌动蛋白丝完整性的能力。AFAP-110和脑特异性亚型AFAP-120（统称为AFAP）在鸡胚脑中以高水平存在。我们试图确定AFAP在小鼠脑中的定位，以确定其表达模式和作为Src家族激酶活性和脑中肌动蛋白丝完整性的细胞调节剂的潜在作用。在E16小鼠胚胎中，AFAP表达水平非常高，集中在嗅球、皮质、前脑、小脑和各种外周感觉结构中。在P3小鼠幼仔中，与E16胚胎相比，总体表达降低，并且AFAP主要在嗅球、皮质和小脑中发现。AFAP表达水平在成年小鼠中显著降低，仅在嗅球中检测到高表达水平。蛋白质印迹分析表明，AFAP的集中表达与AFAP-120同种型密切相关，AFAP-120同种型似乎是AFAP-110的剪接变体。由于AFAP的表达模式与报道的cSrc和Fyn的表达模式重叠，我们假设AFAP定位于调节信号转导级联，直接激活这些非受体酪氨酸激酶和伴随的细胞变化，发生在肌动蛋白丝在大脑发育过程中。(C)2003 Wiley Periodicals，Inc.
The Src family of nonreceptor tyrosine kinases plays an important role in modulating signals that affect growth cone extension, neuronal differentiation, and brain development. Recent reports indicate that the Src SH2/SH3 binding partner AFAP-110 has the capacity to modulate actin filament integrity as a cSrc activating protein and as an actin filament bundling protein. Both AFAP-110 and a brain specific isoform called AFAP-120 (collectively referred to as AFAP) exist at high levels in chick embryo brain. We sought to identify the localization of AFAP in mouse brain in order to identify its expression pattern and potential role as a cellular modulator of Src family kinase activity and actin filament integrity in the brain. In E16 mouse embryos, AFAP expression levels were very high and concentrated in the olfactory bulb, cortex, forebrain, cerebellum, and various peripheral sensory structures. In P3 mouse pups, overall expression was reduced compared to E16 embryos, and AFAP was found primarily in olfactory bulb, cortex, and cerebellum. AFAP expression levels were significantly reduced in adult mice, with high expression levels only detected in the olfactory bulb. Western blot analysis indicated that concentrated expression of AFAP correlates well with the AFAP-120 isoform, which appears to be a splice variant of AFAP-110. As the expression pattern of AFAP overlaps with the reported expression patterns of cSrc and Fyn, we hypothesize that AFAP is positioned to modulate signal transduction cascades that direct activation of these nonreceptor tyrosine kinases and concomitant cellular changes that occur in actin filaments during brain development. (C) 2003 Wiley Periodicals, Inc.