PMID- 31120172
OWN - NLM
STAT- MEDLINE
DCOM- 20200529
LR  - 20211204
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 286
IP  - 18
DP  - 2019 Sep
TI  - Role of the mTOR signalling pathway in salivary gland development.
PG  - 3701-3717
LID - 10.1111/febs.14937 [doi]
AB  - Development of the salivary gland is characterized by extensive branching 
      morphogenesis. Although various molecules have been implicated in salivary gland 
      development, the role of the mammalian target of rapamycin (mTOR) signalling 
      pathway, including both mTOR complexes 1 and 2 (mTORC1 and 2), in salivary gland 
      development is unknown. Here, we examined protein expression levels related to 
      the mTOR signalling pathway using an ex vivo submandibular salivary gland (SMG) 
      organ culture. We showed that branching buds in the salivary glands were 
      substantially decreased and phosphorylation of mTORC1 signalling pathway related 
      proteins (mTOR, p70 ribosomal protein S6 kinase 1 and eukaryotic initiation 
      factor 4E-binding protein 1) was inhibited by rapamycin (an mTOR inhibitor). In 
      addition, AKT, which is an upstream protein kinase of mTORC1 and is downstream of 
      mTORC2, is inhibited by LY294002 (a phosphatidylinositol 3-kinase inhibitor), but 
      not by rapamycin. Moreover, rapamycin-treated ICR neonatal mice exhibited a 
      reduction in both body weight and salivary glands compared with vehicle-treated 
      neonatal mice. The present data indicate that the mTOR signalling pathway, 
      including both mTORC1 and mTORC2, plays a critical role in salivary gland 
      development both in ex vivo SMG organ culture and ICR neonatal mice in vivo.
CI  - (c) 2019 Federation of European Biochemical Societies.
FAU - Sakai, Manabu
AU  - Sakai M
AD  - Department of Clinical Laboratory, Osaka University Dental Hospital, Suita, 
      Japan.
FAU - Fukumoto, Moe
AU  - Fukumoto M
AD  - Department of Cell Biology, National Cerebral and Cardiovascular Center Research 
      Institute, Suita, Japan.
FAU - Ikai, Kazuki
AU  - Ikai K
AD  - Department of Oral-facial Disorders, Osaka University Graduate School of 
      Dentistry, Suita, Japan.
FAU - Ono Minagi, Hitomi
AU  - Ono Minagi H
AD  - Department of Oral-facial Disorders, Osaka University Graduate School of 
      Dentistry, Suita, Japan.
FAU - Inagaki, Shinobu
AU  - Inagaki S
AD  - Department of Child Development & Molecular Brain Science, Osaka University 
      United Graduate School of Child Development, Suita, Japan.
FAU - Kogo, Mikihiko
AU  - Kogo M
AD  - First Department of Oral and Maxillofacial Surgery, Osaka University Graduate 
      School of Dentistry, Suita, Japan.
FAU - Sakai, Takayoshi
AU  - Sakai T
AD  - Department of Oral-facial Disorders, Osaka University Graduate School of 
      Dentistry, Suita, Japan.
LA  - eng
GR  - Challenging Exploratory Research (15K15737)/Japan Society for the Promotion of 
      Science/International
GR  - Scientific Research (A) (15H02575)/Japan Society for the Promotion of 
      Science/International
GR  - Young Scientists (B) (17K17244)/Japan Society for the Promotion of 
      Science/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190603
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Chromones)
RN  - 0 (Morpholines)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Chromones/pharmacology
MH  - Embryo, Mammalian
MH  - Embryonic Development/*genetics
MH  - Mechanistic Target of Rapamycin Complex 1/drug effects
MH  - Mechanistic Target of Rapamycin Complex 2/drug effects
MH  - Mice
MH  - Morphogenesis/genetics
MH  - Morpholines/pharmacology
MH  - Organ Culture Techniques
MH  - Phosphorylation/drug effects
MH  - Salivary Glands/growth & development/*metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - Submandibular Gland/growth & development/*metabolism
MH  - TOR Serine-Threonine Kinases/*genetics
OTO - NOTNLM
OT  - development
OT  - differentiation
OT  - organ culture
OT  - salivary gland
EDAT- 2019/05/24 06:00
MHDA- 2020/05/30 06:00
CRDT- 2019/05/24 06:00
PHST- 2018/12/10 00:00 [received]
PHST- 2019/03/06 00:00 [revised]
PHST- 2019/05/21 00:00 [accepted]
PHST- 2019/05/24 06:00 [pubmed]
PHST- 2020/05/30 06:00 [medline]
PHST- 2019/05/24 06:00 [entrez]
AID - 10.1111/febs.14937 [doi]
PST - ppublish
SO  - FEBS J. 2019 Sep;286(18):3701-3717. doi: 10.1111/febs.14937. Epub 2019 Jun 3.