Sensory and Motor Neuron-derived Factor. A NOVEL HEREGULIN VARIANT HIGHLY EXPRESSED IN SENSORY AND MOTOR NEURONS

doi:10.1074/jbc.270.24.14523

Sensory and Motor Neuron-derived Factor. A NOVEL HEREGULIN VARIANT HIGHLY EXPRESSED IN SENSORY AND MOTOR NEURONS (*)

From the (1)Departments of Protein Chemistry,
(2)Neuroscience, and
(3)Bioanalytical Technologies, Genentech, Inc., South San Francisco, California 94080

^§ To whom correspondence and reprint requests should be addressed:
Dept. of Protein Chemistry, Genentech, Inc., 460 Point San Bruno Blvd., South San Francisco, CA 94080
. Tel.: 415-225-2169; Fax: 415-225-5945; E mail: plo{at}gene.com.

Abstract

The heregulin family of polypeptides arise as splice variants from a single gene and share a conserved epidermal growth factor (EGF)-like domain thought to be the major determinant of their biological activities. We report here the cloning of a novel member of this family, termed sensory and motor neuron-derived factor or SMDF, which is highly expressed in sensory and motor neurons in human and rodent species. It contains a C-terminal β-type EGF-like domain and an unique N-terminal sequence which lacks an Ig-like domain and is distinct from all known heregulin variants. Mammalian cell-expressed SMDF activates tyrosine phosphorylation of a 185-kDa protein in cell lines expressing p185, indicating that it is biologically active. Analyses of expression patterns suggest that, unlike other heregulin variants, SMDF is expressed mainly in the nervous system. In situ hybridization signals with the unique SMDF sequence probe and with a probe to the conserved EGF-like domain are comparable, suggesting that SMDF is the predominant isoform expressed in sensory and motor neurons. Expression of SMDF is maintained in both adult motor neurons and dorsal root ganglion neurons. These findings suggest that SMDF may mediate biological responses such as Schwann cell proliferation and acetylcholine receptor induction in the peripheral nervous system.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank/EMBL Data Bank with accession number(s) L41827.
↵¹ The abbreviations used are:

HRG

heregulin

rHRGβ1

recombinant heregulin β1 amino acid residues 177-241

NDF

Neu differentiation factor

GGF

recombinant human glial growth factor II

ARIA

acetylcholine receptor inducing activity

EGF

epidermal growth factor

nt

nucleotide(s)

bp

base pair(s)

PCR

polymerase chain reaction

KIRA

kinase receptor activation enzyme-linked immunosorbent assay

cpm

counts/min

kb

kilobase(s)

MOPS

4-morpholineethanesulfonic acid.
↵²M. D. Sadick, M. X. Sliwkowski, J. A. Lofgren, and W. L. T. Wong, unpublished results.