Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins.
Using molecular cloning techniques, human homologs of the known members of the trk family of neurotrophin receptors have been cloned and sequenced. Overall, there is a high degree of similarity between the human sequences and those from other mammals; however, there are differences in splicing patterns. There are two spliced forms of the extracellular domain of trkC in the human, a finding that has not been described in other species. In contrast, fewer spliced forms were detected of the intracellular domains of human trkB and trkC than has been described in other mammals. Northern analysis and in situ hybridization experiments indicate that the human trks are expressed in a similar pattern to that described in other mammals. Expression of the trk extracellular domains as fusion proteins with IgG heavy chain yields soluble molecules that mimic intact trks in their binding specificity and affinity. These soluble chimeras block the biological activity of their cognate neurotrophin(s) in vitro.
Shelton
D L
DL
Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080.
Sutherland
J
J
Gripp
J
J
Camerato
T
T
Armanini
M P
MP
Phillips
H S
HS
Carroll
K
K
Spencer
S D
SD
Levinson
A D
AD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004274:DNA, Recombinant; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017403:In Situ Hybridization; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D004274:DNA, Recombinant; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D015335:Molecular Probes; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC