科研之友
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摘要
Different protein kinase C (PKC) isoforms have distinct roles in regulating cell functions. The conventional (alpha, beta, gamma) and novel (delta, epsilon, eta, theta) classes are targets of phorbol ester tumor promoters, which are surrogates of endogenous second messenger, diacylglycerol. The promoter-stimulated disappearance of filopodia was investigated by use of blocking peptides (BPs) that inhibit PKC maturation and/or docking. Filopodia were partially rescued by a peptide representing PKC epsilon hydrophobic sequence, but also by a myristoylated PKC alpha/beta pseudosubstrate sequence, and an inhibitor of T-cell protein tyrosine phosphatase (TC-PTP). The ability to turn over filopodia was widely distributed among PKC isoforms. PKC alpha and eta hydrophobic sequences enhanced filopodia in cells in the absence of tumor promoter treatment. With transcriptional knockdown of PKC alpha, the content of PKC epsilon predominated over other isoforms. PKC epsilon could decrease filopodia significantly in promoter-treated cells, and this was attributed to ruffling. The presence of PKC alpha counteracted the PKC epsilon-mediated enhancement of ruffling. The results showed that there were two mechanisms of filopodia downregulation. One operated in the steady-state and relied on PKC alpha and eta. The other was stimulated by tumor promoters and relied on PKC epsilon. Cycles of protrusion and retraction are characteristic of filopodia and are essential for the cell to orient itself during chemotaxis and haptotaxis. By suppressing filopodia, PKC epsilon can create a long-term "memory" of an environmental signal that may act in nature as a mnemonic device to mark the direction of a repulsive signal.
- 出版日期2017-8
