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首页> 外文期刊>Journal of Cellular Physiology >MEK/ERK pathway mediates PKC activation-induced recruitment of PKCζ and MMP-9 to podosomes
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MEK/ERK pathway mediates PKC activation-induced recruitment of PKCζ and MMP-9 to podosomes

机译：MEK / ERK通路介导PKC activation-induced招聘的PKCζ,MMP-9 podosomes

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摘要

Podosomes are adhesive structures on the ventral surface of cells that invade and degrade the extracellular matrix. Recently, we reported that phorbol 12,13-dibutyrate (PDBu), a protein kinase C (PKC) activator, induced podosome formation in normal human bronchial epithelial (NHBE) cells, and atypical PKCζ regulated MMP-9 recruitment to podosomes for its release and activation. The objective of this study was to explore signaling pathways that are involved in PKC activation-induced podosome formation and matrix degradation. Herein, we found that PDBu increased phosphorylation of PI3K p85, Akt, Src, ERK1/2, and JNK. Inhibitors for PI3K, Akt, and Src suppressed PDBu-induced podosome formation and matrix degradation. In contrast, blockers for MEK/ERK or JNK did not inhibit podosome formation but reduced proteolytic activity of podosomes. Inhibition of PKCζ activity with its pseudosubstrate peptide (PS)-inhibited PDBu-induced phosphorylation of MEK/ERK and JNK. On the other hand, inhibition of MEK/ERK or JNK pathway did not affect PKCζ phosphorylation, but reduced the recruitment of PKCζ and MMP-9 to podosomes. We conclude that PKCζ may regulate MEK/ERK and JNK phosphorylation and in turn activated MEK/ERK and JNK may regulate the proteolytic activity of PDBu-induced podosomes by influencing the recruitment of PKCζ and MMP-9 to podosomes.
机译：在腹侧Podosomes胶粘剂结构表面的细胞入侵和降解细胞外基质。佛波醇12日13-dibutyrate (PDBu),蛋白激酶C (PKC)的激活,诱导podosome形成正常的人类支气管上皮细胞(NHBE),监管和非典型PKCζMMP-9招聘podosomes释放和激活。本研究的目的是探索信号参与PKC途径activation-induced podosome形成和矩阵退化。一种蛋白激酶的磷酸化PI3K p85, Src, ERK1/2,和物。抑制PDBu-induced podosome形成和矩阵退化。MEK / ERK或物没有抑制podosome形成但podosomes蛋白水解活性的降低。抑制PKCζ的活动pseudosubstrate肽(PS)抑制PDBu-induced MEK / ERK的磷酸化和物。另一方面,抑制MEK / ERK或物途径并不影响PKCζ磷酸化,但是降低了招聘的PKCζ,MMP-9podosomes。MEK / ERK和物磷酸化激活MEK / ERK和物可能调节蛋白水解活性PDBu-induced podosomes影响招聘的PKCζ,MMP-9podosomes。

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