Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB.
In vertebrates, the formation and maintenance of neuronal connections are subject to regulation by multiple target-derived, diffusible (neurotrophic) factors. Here we describe the identification and characterization of a novel neurotrophic factor designated neurotrophin-5 (NT-5). NT-5 is structurally related to nerve growth factor and is expressed in embryonic as well as adult tissues. Recombinant NT-5 promotes the survival of peripheral sensory and sympathetic neurons and induces differentiation of the pheochromocytoma cell line PC12. NT-5 activates two trk-related tyrosine kinase receptors and shares these receptors with other neurotrophins. Activation of multiple receptors may permit a single neurotrophin to control target innervation by distinct neuronal populations. Receptor sharing could enable neurotrophic factors emanating from distinct targets to cooperate in regulating neurons with multiple connections.
Berkemeier
L R
LR
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.
Winslow
J W
JW
Kaplan
D R
DR
Nikolics
K
K
Goeddel
D V
DV
Rosenthal
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000302:isolation & purification; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D020917:Receptor, trkA; D011994:Recombinant Proteins
D008565:Membrane Proteins; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D011994:Recombinant Proteins; C071951:neurotrophin 5; D004247:DNA; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA