EARLY CHANGES IN PROTEIN-SYNTHESIS INDUCED BY BASIC FIBROBLAST GROWTH-FACTOR, NERVE GROWTH-FACTOR, AND EPIDERMAL GROWTH-FACTOR IN PC12 PHEOCHROMOCYTOMA CELLS

Nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) st imulate neuronal differentiation, whereas epidermal growth factor (EGP ) promotes only mitogenic responses in PC12 pheochromocytoma cells. Th e early changes in protein synthesis induced by bFGF, NGF, and EGF in these cells have been determined by two-dimensional PAGE of [S-35]meth ionine-labeled proteins and computerized image analysis. The rate of s ynthesis of only 29 proteins (out of approximate to 1500 identified) w as found to be modulated during the first several hours of growth fact or stimulation. Individually, 12 were affected by EGF, 23 were affecte d by bFGF, and 20 were affected by NGF. Eight of these were regulated by all three growth factors, while 10 proteins were commonly induced b y bFGF and NGF, in accordance with the essentially identical morpholog ical responses induced by these two factors. In addition, the effects of bFGF and NGF were about equally divided between increases and decre ases in the rate of synthesis of individual proteins, whereas EGF caus ed significantly more positive (increased) responses. All proteins mod ulated by NGF or FGF alone were negative in their response and those i nduced by only EGF were positive. Of particular interest, the rate of synthesis of two proteins of 55 kDa and pI 5.45 and 5.50 was dramatica lly and transiently induced during the first 2 hr of bFGF and NGF trea tment and was not affected by EGF. This study indicates that all three factors elicit early increases and decreases in the synthesis of a qu ite limited number of proteins and provides molecular evidence for the specificity of a differentiative vs. a proliferative growth factor-in duced signaling pathway in these cells.