Expression of functional TrkA receptor tyrosine kinase in the HMC-1 human mast cell line and in human mast cells.
Expression of functional TrkA receptor tyrosine kinase in the HMC-1 human mast cell line and in human mast cells.
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DOI：
10.1182/blood.v90.5.1807
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发表时间：
1997-09
期刊：
影响因子：
20.3
通讯作者：
S. Tam;M. Tsai;M. Yamaguchi;K. Yano;Joseph H. Butterfield;Stephen J. Galli
中科院分区：
文献类型：
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作者：
S. Tam;M. Tsai;M. Yamaguchi;K. Yano;Joseph H. Butterfield;Stephen J. Galli
神经生长因子（NGF）可通过与肥大细胞上的受体相互作用影响肥大细胞的发育和功能。我们现在报告的鉴定全长酪氨酸激酶的trkA，trkB和trkC神经营养因子受体基因在HMC-1人肥大细胞白血病细胞的mRNA转录。虽然HMC-1细胞缺乏p75 mRNA，但它们表达了缺失外显子的trkA剪接变体（trkAI）、截短的trkB（trkB.T1）和截短的trkC的转录本。通过流式细胞术，HMC-1细胞表现出表达TrkA，TrkB和TrkC受体蛋白，含有全长酪氨酸激酶结构域。HMC-1细胞的NGF刺激诱导TrkA蛋白的酪氨酸磷酸化，早期反应基因c-fos和NGF 1-A的表达增加，以及ERK-促分裂原活化蛋白（MAP）激酶的活化，结果表明HMC-1细胞中的TrkA受体是完全功能性的。高度纯化的人肺肥大细胞表达trkA、trkB和trkC的mRNA，而人脐带血来源的肥大细胞表达trkA和trkC的mRNA，但不表达trkB。此外，人脐带血来源的未成熟肥大细胞的制剂不仅表达TrkA的mRNA转录物和蛋白质，而且在添加NGF到其培养基中3周后显示出显着更高数量的糜酶阳性细胞。此外，HMC-1细胞表达NGF、脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3）的mRNA，这些mRNA是TrkA、TrkB和TrkC的同源配体，而在人脐带血肥大细胞制剂中可检测到NGF和BDNF转录本。总之，我们的研究结果表明，人肥大细胞表达功能性TrkA受体酪氨酸激酶，并表明，神经生长因子可能能够促进肥大细胞发育和/或成熟的某些方面在人类。我们的研究还提出了人类肥大细胞可能是神经营养因子的潜在来源的可能性。
Nerve growth factor (NGF) can influence mast cell development and function in murine rodents by interacting with its receptors on mast cells. We now report the identification of mRNA transcripts of full-length tyrosine kinase-containing trkA, trkB, and trkC neurotrophin receptor genes in HMC-1 human mast cell leukemia cells. Although HMC-1 cells lacked p75 mRNA, they expressed transcripts for the exon-lacking splice variant of trkA (trkAI), truncated trkB (trkB.T1), and truncated trkC. By flow cytometry, HMC-1 cells exhibited expression of TrkA, TrkB, and TrkC receptor proteins containing full-length tyrosine kinase domains. NGF stimulation of HMC-1 cells induced tyrosine phosphorylation of TrkA protein, increased expression of the early response genes c-fos and NGF1-A, and activation of ERK-mitogen-activated protein (MAP) kinase, results which indicate that TrkA receptors in HMC-1 cells are fully functional. Highly purified populations of human lung mast cells expressed mRNAs for trkA, trkB and trkC, whereas preparations of human umbilical cord blood-derived mast cells expressed mRNAs for trkA and trkC, but not trkB. Moreover, preparations of human umbilical cord blood-derived immature mast cells not only expressed mRNA transcript and protein for TrkA, but exhibited significantly higher numbers of chymase-positive cells after the addition of NGF to their culture medium for 3 weeks. In addition, HMC-1 cells expressed mRNAs for NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), the cognate ligands for TrkA, TrkB, and TrkC, whereas NGF and BDNF transcripts were detectable in human umbilical cord blood mast cell preparations. Taken together, our findings show that human mast cells express a functional TrkA receptor tyrosine kinase and indicate that NGF may be able to promote certain aspects of mast cell development and/or maturation in humans. Our studies also raise the possibility that human mast cells may represent a potential source for neurotrophins.