Involvement of p44/p42 MAP kinase in insulin-like growth factor-I-induced alkaline phosphatase activity in osteoblast-like-MC3T3-E1 cells

• Published in: Molecular and cellular endocrinology 2006-06, Vol.251 (1), p.42-48
• Main Authors: Hanai, Yoshiteru, Tokuda, Haruhiko, Ishisaki, Akira, Matsushima-Nishiwaki, Rie, Nakamura, Norimi, Yoshida, Minoru, Takai, Shinji, Ohta, Toshiki, Kozawa, Osamu
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Alkaline phosphatase; Alkaline Phosphatase - metabolism; Animals; IGF-I; Insulin-Like Growth Factor I - metabolism; JNK Mitogen-Activated Protein Kinases - metabolism; Mice; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Osteoblast; Osteoblasts; p38 Mitogen-Activated Protein Kinases - metabolism; p44/p42 MAP kinase; Phosphorylation
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2006.02.014

It has been shown that insulin-like growth factor-I (IGF-I) stimulates the activity of alkaline phosphatase, a marker of mature osteoblast phenotype, in osteoblasts. In the present study, we investigated the involvement of the mitogen-activated protein (MAP) kinase superfamily in the IGF-I-stimulated alkaline phosphatase activity in osteoblast-like MC3T3-E1 cells. IGF-I-stimulated alkaline phosphatase activity dose dependently in the range between 1 nM and 0.1 μM. IGF-I induced the phosphorylation of p44/p42 MAP kinase and p38 MAP kinase but not stress-activated protein kinase/c- Jun N-terminal kinase (SAPK/JNK). PD98059 and U0126, specific inhibitors of the upstream kinase that activates p44/p42 MAP kinase, significantly suppressed the IGF-I-induced alkaline phosphatase activity. On the contrary, SB203580 and PD169316, specific inhibitors of p38 MAP kinase, failed to affect the activity induced by IGF-I. Specific inhibitors for phosphatidylinositol 3-kinase (PI3K)/Akt pathway (LY294002 and wortmannin) also had no significant effect on IGF-I-induced p44/p42 MAP kinase phosphorylation. The phosphorylation of p44/p42 MAP kinase induced by IGF-I was reduced by U0126. These results strongly suggest that p44/p42 MAP kinase among the MAP kinase superfamily plays a role in the IGF-I-stimulated alkaline phosphatase activity in osteoblast-like MC3T3-E1 cells.