Structure, expression and function of a schwannoma-derived growth factor

Abstract

During the development of the nervous system, cells require growth factors that regulate their division and survival. To identify new growth factors, serum-free growth-conditioned media from many clonal cell lines were screened for the presence of mitogens for central nervous system glial cells. A cell line secreting a potent glial mitogen was established from a tumour (or 'schwannoma') derived from the sheath of the sciatic nerve. The cells of the tumour, named JS1 cells, were adapted to clonal culture and identified as Schwann cells. Schwann cells secrete an autocrine mitogen and human schwannoma extracts have mitogenic activity on glial cells. Until now, neither mitogen has been purified. Here we report the purification and characterization of a mitogenic molecule, designated schwannoma-derived growth factor (SDGF), from the growth-conditioned medium of the JS1 Schwann cell line. SDGF belongs to the epidermal growth factor family, and is an autocrine growth factor as well as a mitogen for astrocytes, Schwann cells and fibroblasts.

Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tryosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4

“…One such group of ligands binds speci®cally to and activates EGFR but does not interact directly with ErbB-2, ErbB-3 or ErbB-4. These include epidermal growth factor (EGF) (Savage et al, 1972), transforming growth factor-a (TGF-a) (Marquardt et al, 1984), amphiregulin (AR) (Shoyab et al, 1989), also known as a schwanoma derived growth factor (Kimura et al, 1990) or keratinocyte autocrine growth factor (Cook et al, 1991), heparin binding-EGF likegrowth factor (HB-EGF) (Higashiyama et al, 1991), and betacellulin (Shing et al, 1993).…”

Expression of Neuregulins and their Putative Receptors, ErbB2 and ErbB3, Is Induced during Wallerian Degeneration

“…It is interesting that although neuregulin mRNA was undetectable in noninjured nerve, neuregulin mRNA is induced by 7 d postaxotomy to levels comparable to that seen in spinal cord, a tissue previously reported to demonstrate some of the highest levels of neuregulin mRNA expression in the body (Wen et al, 1992). As a control, this blot also contained RNA from the rat JS1 schwannoma cell line, a line derived from a tumor induced by in utero chemical mutagenesis (Schubert et al, 1974;Kimura et al, 1990). The absolute highest abundance of neuregulin mRNA that we observed was in the JS1 cell line (Fig.…”

New gene, nel, encoding a Mr 93 K protein with EGF‐like repeats is strongly expressed in neural tissues of early stage chick embryos

“…Several other growth factors related to EGF were identified (Todaro et al, 1980;Blomquist et al, 1984;Shoyab et al, 1989;Kimura et al, 1990).…”