Lysophosphatidylcholine Mediates Melanocyte Dendricity through PKCζ Activation
Melanocytes photoprotect the skin through transfer of melanin-containing melanosomes to keratinocytes. Factors that increase melanocyte dendricity increase melanosome transfer, and are important for prevention of skin cancer. Secretory phospholipase-A2 type X (sPLA2-X) is released by epidermal kerat...
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Veröffentlicht in: | Journal of investigative dermatology 2007-03, Vol.127 (3), p.668-675 |
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Sprache: | eng |
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Zusammenfassung: | Melanocytes photoprotect the skin through transfer of melanin-containing melanosomes to keratinocytes. Factors that increase melanocyte dendricity increase melanosome transfer, and are important for prevention of skin cancer. Secretory phospholipase-A2 type X (sPLA2-X) is released by epidermal keratinocytes and we have shown that lysophosphatidylcholine (LPC), the main lysophospholipid released in response to sPLA2-X activity, stimulates melanocyte dendricity. LPC activates protein kinase C (PKC) and increases cAMP in other cells. Treatment of melanocytes with sPLA2-X or LPC induced phosphorylation of the ζ isoform of PKC, and inhibition of protein kinase C zeta (PKCζ) activity abrogated LPC-dependent dendricity. We have shown previously that the guanosine triphosphate-binding proteins Rac and Rho link hormone signaling and dendricity in melanocytes. Treatment of melanocytes with LPC induced rapid activation of Rac that peaked at 30minutes; Rho was also activated, but peaked earlier and declined faster. Through the use of constitutively active mutants of Rac, we show that PKCζ activation is downstream of Rac. We conclude that the primary signaling pathway for LPC-dependent dendrite formation in human melanocytes involves the activation of PKCζ and that PKCζ phosphorylation is Rac dependent. Downstream mediators of LPC-dependent dendricity include Rac and Rho. |
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ISSN: | 0022-202X 1523-1747 |
DOI: | 10.1038/sj.jid.5700567 |