TY - JOUR
T1 - Enhancement or induction of neurite formation by a protein tyrosine phosphatase inhibitor, 3,4-dephostatin, in growth factor-treated PC12h cells
AU - Fujiwara, Sari
AU - Watanabe, Takumi
AU - Nagatsu, Toshiharu
AU - Gohda, Jin
AU - Imoto, Masaya
AU - Umezawa, Kazuo
PY - 1997/9/8
Y1 - 1997/9/8
N2 - We studied the effect of the 3,4 dihydroxy analogue of dephostatin (3,4-dephostatin), an inhibitor of protein-tyrosine phosphatase (PTPase), on the differentiation of rat pheochromocytoma PC12 cells. 3,4-Dephostatin accelerated NGF-induced neurite formation in PC12h cells, a subline of PC12 cells, whereas the inhibitor alone did not induce neurite formation. It sustained the NGF-induced tyrosine phosphorylation of several proteins, most prominently that of mitogen-activated protein (MAP) kinase. EGF alone did not induce differentiation in PC12h cells, but it induced neurite formation in the presence of 3,4-dephostatin. The inhibitor also prolonged EGF-induced tyrosine phosphorylation and activation of MAP kinase. An inactive analogue of dephostatin, 2'-O-methyl-dephostatin showed no effect on either neurite formation or MAP kinase tyrosine phosphorylation in NGF- or EGF-treated PC12h cells. Thus, we demonstrated that the PTPase inhibitor could enhance growth factor-induced differentiation in PC12 cells possibly by sustaining the MAP kinase activity.
AB - We studied the effect of the 3,4 dihydroxy analogue of dephostatin (3,4-dephostatin), an inhibitor of protein-tyrosine phosphatase (PTPase), on the differentiation of rat pheochromocytoma PC12 cells. 3,4-Dephostatin accelerated NGF-induced neurite formation in PC12h cells, a subline of PC12 cells, whereas the inhibitor alone did not induce neurite formation. It sustained the NGF-induced tyrosine phosphorylation of several proteins, most prominently that of mitogen-activated protein (MAP) kinase. EGF alone did not induce differentiation in PC12h cells, but it induced neurite formation in the presence of 3,4-dephostatin. The inhibitor also prolonged EGF-induced tyrosine phosphorylation and activation of MAP kinase. An inactive analogue of dephostatin, 2'-O-methyl-dephostatin showed no effect on either neurite formation or MAP kinase tyrosine phosphorylation in NGF- or EGF-treated PC12h cells. Thus, we demonstrated that the PTPase inhibitor could enhance growth factor-induced differentiation in PC12 cells possibly by sustaining the MAP kinase activity.
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U2 - 10.1006/bbrc.1997.7174
DO - 10.1006/bbrc.1997.7174
M3 - Article
C2 - 9299481
AN - SCOPUS:0031559856
VL - 238
SP - 213
EP - 217
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -