Isoforms of the avian TrkC receptor: a novel kinase insertion dissociates transformation and process outgrowth from survival.
TrkC receptor isoforms have been identified by cDNA cloning and RT-PCR analysis of embryonic chick brain RNA. An N-terminal truncation motif is missing from the signal sequence and first cysteine cluster of the extracellular domain. Within the cytoplasmic dimain, a kinase truncation motif retains part of the kinase domain, but appeared to lack activity. Finally, a kinase insert (KI) motif introduces a 25 amino acid sequence distinct from the known mammalian inserts. KI receptors, like full-length receptors, were tyrosine phosphorylated in response to NT-3 and mediated the transformation of chick embryo fibroblasts and process outgrowth from rat PC12 cells. However, KI receptors supported little, if any, survival of serum-deprived PC12 cells. These results indicate that alternative splicing of trkC transcripts is an important mechanism for regulating cellular responses to NT-3.
Garner
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AS
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4975.
Large
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TH
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D002645:Chickens; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D008969:Molecular Sequence Data; D016501:Neurites; D016716:PC12 Cells / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry*; D020812:Receptor, trkC; D017978:Receptors, Growth Factor / Q000737:chemistry*; D013329:Structure-Activity Relationship
D018076:DNA, Complementary; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC