Characterization of a neuregulin-related gene, Don-1, that is highly expressed in restricted regions of the cerebellum and hippocampus.
Members of the epidermal growth factor family of receptors have long been implicated in the pathogenesis of various tumors, and more recently, apparent roles in the developing heart and nervous system have been described. Numerous ligands that activate these receptors have been isolated. We report here on the cloning and initial characterization of a second ligand for the erbB family of receptors. This factor, which we have termed Don-1 (divergent of neuregulin 1), has structural similarity with the neuregulins. We have isolated four splice variants, two each from human and mouse, and have shown that they are capable of inducing tyrosine phosphorylation of erbB3, erbB4, and erbB2. In contrast to those of neuregulin, high levels of expression of Don-1 are restricted to the cerebellum and dentate gyrus in the adult brain and to fetal tissues.
Busfield
S J
SJ
Millennium Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139, USA. busfield@mpi.com
Michnick
D A
DA
Chickering
T W
TW
Revett
T L
TL
Ma
J
J
Woolf
E A
EA
Comrack
C A
CA
Dussault
B J
BJ
Woolf
J
J
Goodearl
A D
AD
Gearing
D P
DP
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002531:Cerebellum / Q000502:physiology*; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003001:Cloning, Molecular; D015870:Gene Expression; D008040:Genetic Linkage; D006023:Glycoproteins / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics*; D020880:Neuregulins; D019000:Phosphotyrosine / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D006023:Glycoproteins; D008024:Ligands; D008565:Membrane Proteins; C106766:NRG2 protein, human; D009414:Nerve Growth Factors; D020880:Neuregulins; C491453:Nrg2 protein, mouse; D017978:Receptors, Growth Factor; D019000:Phosphotyrosine