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首页> 外文期刊>Journal of Cellular Physiology >Receptor-mediated effects on ligand availability influence relative mitogenic potencies of epidermal growth factor and transforming growth factor alpha.
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Receptor-mediated effects on ligand availability influence relative mitogenic potencies of epidermal growth factor and transforming growth factor alpha.

机译：对配体受体介导的影响可用性影响相对促有丝分裂的效力表皮生长因子和改变增长系数α。

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Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) elicit quantitatively different cell proliferation responses even though they act via a common receptor, the epidermal growth factor receptor (EGFR). We hypothesized that differential cellular trafficking of available ligand is responsible for the different mitogenic responses elicited by EGF and TGF alpha. Mitogenesis and ligand depletion were determined simultaneously in NR6 mouse fibroblasts expressing either wild-type (WT) or internalization-deficient cytoplasmic domain-truncated (c'973) EGFR. Thus we could determine the effects of both ligand-induced and low level constitutive ligand/receptor processing. For a given initial amount of growth factor, TGF alpha is a weaker stimulus than EGF in cells expressing either form of the EGFR. This difference in the mitogenic potencies correlates with increased depletion of TGF alpha observed during the growth assays. When this difference in ligand depletion is accounted for, or minimized, EGF and TGF alpha elicit quantitatively similar growth responses. Therefore, the relative mitogenic potencies of EGF and TGF alpha depend on ligand availability, as determined by the cellular trafficking of these ligands in conjunction with environmental circumstances. Interestingly, our data demonstrate that TGF alpha can be a less potent mitogenic stimulus than EGF under conditions where ligand availability is limited. Further, in our assays, differences in ligand processing are sufficient to explain the different mitogenic potencies of these growth factors in either of the receptor trafficking scenarios. Our results suggest a model of regulation of hormone responsiveness which favors dissociative ligands (such as TGF alpha) in receptor-limited situations and non-dissociative ligands (such as EGF) in the face of high receptor levels.
机译：表皮生长因子(EGF)和转换生长因子α(转化生长因子α)引起定量不同细胞增殖反应,尽管他们通过一个共同的行动受体、表皮生长因子受体(EGFR)。细胞贩运可用的配体负责不同的促有丝分裂的反应引起表皮生长因子和转化生长因子α。配体消耗同时测定在NR6小鼠成纤维细胞表达野生型(WT)或internalization-deficient表皮生长因子受体细胞质domain-truncated 973 (c)。我们可以确定的影响ligand-induced本构和低水平配体/受体处理。生长因子、转化生长因子α是较弱的比EGF刺激细胞中的表达形式表皮生长因子受体。的效能与损耗的增加转化生长因子α观察期间增长分析。这种差异在配体损耗占或最小化,表皮生长因子和转化生长因子α引起定量类似的增长反应。因此,相对的促有丝分裂的效力表皮生长因子和转化生长因子α取决于配体可用性,由细胞贩运这些配体与环境环境。证明转化生长因子α可以不那么有效促有丝分裂的比条件下EGF刺激在配体可用性是有限的。我们的化验,配体的差异处理足以解释不同的促有丝分裂的这些生长因子的效力的受体贩卖场景。建议的模型调节激素响应性有利于离解配体在receptor-limited(如转化生长因子α)情况和non-dissociative配体(如EGF)面对高受体水平。

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