Histamine, a primary mediator of allergic responses, elicits its effects by activating specific receptors belonging to the GPCR family in target cells. Activation of histamine receptor can activate MAP kinases as recorded by monitoring the phosphorylation of extracellular signal regulated kinase (ERK). Despite this, ERK phosphorylation does not translate into pro-proliferative changes after histamine stimulation in HeLa cells. Here we show that histamine H1 receptor activation mediates MAPK activation through PLCβ, Src, PKCδ and MEK pathway, but does not lead to nuclear relocalization of phospho-ERK (pERK), classically associated with pro-proliferative changes. Live cell imaging, FRET and FRAP measurements along with functional analysis reveal that pERK generated by histamine activation is physically and functionally restricted in the cytosol and the findings report a spatial regulation of MAPK cascade activated non-canonically through GPCRs unlike its canonical activation by EGF.

中文翻译：

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通过组胺H1受体激活的ERK通过细胞溶质中的空间限制而具有抗增殖作用。

组胺是过敏反应的主要介质，它通过激活靶细胞中属于GPCR家族的特定受体来引起其作用。如通过监测细胞外信号调节激酶（ERK）的磷酸化所记录的，组胺受体的激活可以激活MAP激酶。尽管如此，在HeLa细胞中组胺刺激后，ERK磷酸化不会转化为增殖增生变化。在这里，我们显示组胺H1受体激活通过PLCβ，Src，PKCδ和MEK途径介导MAPK激活，但不会导致磷酸化ERK（pERK）的核再定位，这通常与促增殖变化相关。活细胞成像