Transforming growth factor alpha and a PC12-derived growth factor induce neurites in PC12 cells and enhance the survival of embryonic brain neurons.

Abstract

We have identified and characterized a 5000-Da protein that induces neurite outgrowth from PC12 pheochromocytoma cells, enhances the survival of embryonic rat brain neurons in primary culture, and induces the multiplication of embryonic rat brain astrocytes in primary culture. The factor is produced by a flat cell PC12 variant that expresses the activated ras oncogene after transfection of the gene. The factor resembles transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) in that it induces anchorage-independent colony formation of normal rat kidney cells in soft agar and competes with EGF for binding to the EGF receptor. Rat TGF alpha and human TGF alpha also induce neurite outgrowth from PC12 and enhance the survival of embryonic brain neurons. The PC12 variant-derived factor can be distinguished from TGF alpha and EGF immunologically and by migration rates on reversed-phase high-performance liquid chromatography.

K252a potentiates epidermal growth factor‐induced differentiation of PC12 cells

“…The role of the receptor autophosphorylation in EGF-induced signal transduction is not clear (e.g., Lichtner et al, 1992). Several serine and threonine residues of the receptor also become phosphorylated under various conditions and such phosphorylation can reduce the receptor tyrosine kinase activity (Schlessinger, 1988;Yarden and Ullrich, 1988;Carpenter and Cohen, 1990), Zhang et al (1990) reported that transforming growth factor-a (TGF-a), which also acts via the EGF receptor, induced the neuronal differentiation of PC12 pheochromocytoma cells in that it caused the cells to extend short neurites; EGF was found to produce a morphologically similar effect by these authors. Recently, Sano and Kitajima (1992) and Nakafuku and Kaziro (1993) also reported that EGF induces short neurites in PC12 cells.…”

“…The ability of EGF to induce even short neurites in PC12 (Zhang et al, 1990;Sano and Kitajima, 1992;Nakafuku and Kaziro, 1993) is something of a surprise because others have reported that PC 12 cells respond to EGF but not by neurite outgrowth (Huff and Guroff, 1979;Chandler and Henchman, 1980;Boonstra et a]., 1983). This apparent discrepancy was ascribed to differences in the PC12 cell lines used (Zhang et al, 1990) or culture conditions (Nakafuku and Kaziro, 1993).…”

“…This apparent discrepancy was ascribed to differences in the PC12 cell lines used (Zhang et al, 1990) or culture conditions (Nakafuku and Kaziro, 1993).…”

Prenatal ontogeny of the epidermal growth factor receptor and its ligand, transforming growth factor alpha, in the rat brain

“…EGF and TGFa have been shown to induce process outgrowth and enhance cell survival in primary cultures of postmitotic neurons from a variety of brain areas (Morrison et al, 1987(Morrison et al, , 1988Abe et al, 1990;Kornblum et al, 1990;Zhang et al, 1990). Additionally, the presence of EGF in culture media can influence the expression of region-specific markers in cortical neurons in vitro (Ferri and Levitt, 1995).…”

“…Indeed, numerous studies in vitro have supported these conclusions. Both EGF and TGFa influence the survival and differentiation of postmitotic CNS neurons in a variety of systems, including neurons derived from the postnatal basal ganglia (Morrison et al, 1987), from embryonic and postnatal neocortex (Abe et al, 1990;Zhang et al, 1990;Kornblum et al, 1990) and dopaminergic neurons from embryonic midbrain (Casper et al, 1991;Alexi and Hefti, 1993). EGF and TGFa have also been shown to induce the proliferation of cultured CNS astrocytes (Leutz and Schachner, 1981), as well as to influence oligodendrocyte differentiation (Almazan et al, 1985;Sheng et al, 1989).…”