2003 Fiscal Year Final Research Report Summary
Role of integrin and EGF in organogenesis of salivary gland
| Project/Area Number |
13671949
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | ASAHI UNIVERSITY |
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Principal Investigator |
KASHIMATA Masanori Asahi University, Dental Pharmacology, Professor, 歯学部, 教授 (30152630)
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| Project Period (FY) |
2001 – 2003
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| Keywords | EGF / EGFR / Erk / PLCγ1 / PKC / PI3K / Branching / Morphogenesis |
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| Research Abstract |
Branching morphogenesis of fetal mouse submandibular glands (SMGs) partly depends on the EGF receptor that triggers at least three intracellular signaling pathways involving the ERK-1/2, PLCγ1, and PI3K. Western blotting revealed that PLCγ1 is present from E13 to E18 but drops of f precipitously to negligible levels on the day of birth and thereafter, and PI3K, PKB(Akt), and several PKC isozymes are expressed from E13 onward through adult life. Both PLCγ1 and PI3K are phosphorylated in response to EGF. Inhibition of PI3K by LY294002 inhibited EGF-stimulated branching, but inhibition of PLCgammal by U73122 had no effect. Western blotting showed that the concentrations of 8 PKC isozymes vary with age in the fetal and postnatal SMG. However, general inhibition of PKCs by Calphostin C or specific inhibition of PKCα or of PKCε by Go6976 or Ro-32-0432, respectively, increased EGF-stimulated branching. Calphostin C also increased EGF-stimulated phosphorylation of ERK-1/2. These findings indicate that signaling from the EGF receptor in the fetal mouse SMG varies with development and triggers stimulatory effects by means of ERK-112 and PI3K but inhibitory effects by means of PKC isozymes.
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[Publications] Koyama, N., Kashimata, M., Sakashita, H., Sakagami, H., Gresik, E.: "EGF-stimulated signaling by mean of PI3K, PLCg1, and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular glands"Developmental Dynamics. 227. 216-226 (2003)
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