PMID- 15895362
OWN - NLM
STAT- MEDLINE
DCOM- 20060111
LR  - 20211203
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 205
IP  - 3
DP  - 2005 Dec
TI  - Negative regulation of melanogenesis by phospholipase D1 through mTOR/p70 S6 
      kinase 1 signaling in mouse B16 melanoma cells.
PG  - 444-51
AB  - Melanogenesis is a principal parameter of differentiation in melanocytes and 
      melanoma cells. Our recent study has demonstrated that phospholipase D1 (PLD1) 
      regulates the melanogenic signaling through modulating the expression of 
      tyrosinase, the rate-limiting step enzyme in the melanin biosynthesis. The 
      current study was designed to gain more insight into the involvement of PLD1 in 
      the regulation of melanogenesis. To investigate the role of PLD1, we examined the 
      effect of knockdown of endogenous PLD1 by small interference RNA (siRNA) on 
      melanogenesis in B16 melanoma cells. It was shown that the melanin synthesis was 
      induced in PLD1-knockdowned cells, and also that the level of melanin synthesis 
      was well correlated with increases in expression level of tyrosinase and its 
      related proteins (Tyrp1 and Dct). Furthermore, the reduction of expression levels 
      of PLD1 by siRNA transfection was accompanied by diminution of ribosomal S6 
      kinase 1 (S6K1) phosphorylation. The activity of mammalian target of rapamycin 
      (mTOR) is essential for phosphorylation of S6K1 and the treatment malanoma cells 
      with rapamycin, a potent inhibitor of mTOR effectively induced melanogenesis. The 
      results obtained here provide possible evidence that PLD1 exerts a negative 
      regulatory role in the melanogenic process through mTOR/S6K1 signaling.
CI  - (c) 2005 Wiley-Liss, Inc.
FAU - Ohguchi, Kenji
AU  - Ohguchi K
AD  - Gifu International Institute of Biotechnology, Kakamigahara, Gifu, Japan. 
      kohguchi@giib.or.jp
FAU - Banno, Yoshiko
AU  - Banno Y
FAU - Nakagawa, Yoshihito
AU  - Nakagawa Y
FAU - Akao, Yukihiro
AU  - Akao Y
FAU - Nozawa, Yoshinori
AU  - Nozawa Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Melanins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (protein kinase modulator)
RN  - EC 1.14.18.1 (Monophenol Monooxygenase)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - EC 3.1.4.4 (phospholipase D1)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Intracellular Signaling Peptides and Proteins/pharmacology
MH  - Melanins/*antagonists & inhibitors/*biosynthesis
MH  - Melanoma/*metabolism/pathology
MH  - Mice
MH  - Monophenol Monooxygenase/metabolism
MH  - Phospholipase D/genetics/*physiology
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/drug effects/*metabolism
MH  - RNA, Small Interfering/genetics/pharmacology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - Signal Transduction/*physiology
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Transfection
EDAT- 2005/05/17 09:00
MHDA- 2006/01/13 09:00
CRDT- 2005/05/17 09:00
PHST- 2005/05/17 09:00 [pubmed]
PHST- 2006/01/13 09:00 [medline]
PHST- 2005/05/17 09:00 [entrez]
AID - 10.1002/jcp.20421 [doi]
PST - ppublish
SO  - J Cell Physiol. 2005 Dec;205(3):444-51. doi: 10.1002/jcp.20421.