Overexpression of striatal enriched phosphatase (STEP) promotes the neurite outgrowth induced by a cAMP analogue in PC12 cells.
A cytoplasmic protein tyrosine phosphatase (PTPase) designated as striatal enriched phosphatase with a molecular weight of 46 kDa (STEP46) is highly expressed in striatal neurons with dopamine D1-receptors. To examine the hypothesis that STEP46 is involved in the neuronal functions modulated by the cyclic adenosine 3', 5'-monophosphate (cAMP)-signaling system, we introduced the complementary DNA of STEP46 into the pheochromocytoma cell line PC12, which exhibits neuronal differentiation characterized by neurite outgrowth in response to cAMP and nerve growth factor stimulation, and we established subclonal cell lines that constitutively overexpress STEP46 protein with PTPase activity. The subclones expressing STEP46 showed increased neurite outgrowth during differentiation induced by a cAMP analogue (dibutyryl cAMP). The positive regulatory role of STEP46 in the cAMP-induced neuronal differentiation of PC12 cells indicates that STEP46 may play a role in neuronal processes modulated by the cAMP-signaling cascade as a PTPase.
Okamura
A
A
Laboratory of Neurobiology, Department of Neurosurgery, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Goto
S
S
Nishi
T
T
Hamasaki
T
T
Ushio
Y
Y
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000201:enzymology*; D000242:Cyclic AMP / Q000378:metabolism; D015342:DNA Probes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic; D007546:Isoquinolines / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000201:enzymology*; D016716:PC12 Cells; D010957:Plasmids; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000235:genetics*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013449:Sulfonamides; D014162:Transfection
D015342:DNA Probes; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D003994:Bucladesine; D000242:Cyclic AMP; D017027:Protein Tyrosine Phosphatases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide