Overexpression of striatal enriched phosphatase (STEP) promotes the neurite outgrowth induced by a cAMP analogue in PC12 cells

• Published in: Brain research. Molecular brain research. 1999-04, Vol.67 (1), p.1-9
• Main Authors: Okamura, Akira, Goto, Satoshi, Nishi, Toru, Hamasaki, Tadashi, Ushio, Yukitaka
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bucladesine - pharmacology; Corpus Striatum - enzymology; Cyclic AMP; Cyclic AMP - metabolism; Cyclic AMP-dependent protein kinase; DNA Probes; Enzyme Inhibitors - pharmacology; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic; Isolated neuron and nerve. Neuroglia; Isoquinolines - pharmacology; Neurites - drug effects; Neurites - enzymology; PC12; PC12 Cells; Plasmids; Protein tyrosine phosphatase; Protein Tyrosine Phosphatases - analysis; Protein Tyrosine Phosphatases - genetics; Rats; Signal Transduction - physiology; Striatum; Sulfonamides; Transfection; Vertebrates: nervous system and sense organs
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/S0169-328X(99)00003-0

A cytoplasmic protein tyrosine phosphatase (PTPase) designated as striatal enriched phosphatase with a molecular weight of 46 kDa (STEP 46) is highly expressed in striatal neurons with dopamine D1-receptors. To examine the hypothesis that STEP 46 is involved in the neuronal functions modulated by the cyclic adenosine 3′,5′-monophosphate (cAMP)-signaling system, we introduced the complementary DNA of STEP 46 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 STEP 46 protein with PTPase activity. The subclones expressing STEP 46 showed increased neurite outgrowth during differentiation induced by a cAMP analogue (dibutyryl cAMP). The positive regulatory role of STEP 46 in the cAMP-induced neuronal differentiation of PC12 cells indicates that STEP 46 may play a role in neuronal processes modulated by the cAMP-signaling cascade as a PTPase.