Molecular and biochemical characterization of the human trk proto-oncogene
Molecular analysis of the human irk oncogene, a transforming gene isolated from a colon carcinoma biopsy, revealed the existence of a novel member of the tyrosine kinase gene family. This locus, which the authors now designate the trk proto-oncogene, codes for a protein of 790 amino acid residues that has several features characteristic of cell surface receptors. They include (i) a 32-amino-acid-long putative signal peptide, (ii) an amino-terminal moiety (residues 33 to 407) rich in consensus sites for N-glycosylation, (iii) a transmembrane domain, (iv) a kinase catalytic region highly related to that of other tyrosine kinases, and (v) a very short (15 residue) carboxy-terminal tail. Residues 1 to 392 were absent in the trk oncogene, as they were replaced by tropomyosin sequences. However, no other differences were found between the transforming and nontransforming trk alleles (residues 392 to 790), suggesting that no additional mutations are required to activate the transforming potential of this gene. The human trk proto-oncogene codes for a 140,000-dalton glycoprotein, designated gp140/sup proto-trk/. However, its primary translational product is a 110,000-dalton glycoprotein which becomes immediately glycosylated, presumably during its translocation into the endoplasmic reticulum. This molecule, designated gp110/sup proto-trk/, is further glycosylated to yield the mature form, gp140/sup proto-trk/. Both gp110/sup proto-trk/ and gp140/sup proto-trk/ proteins possess in vitro kinase activity specific for tyrosine residues. Finally, iodination of intact N1H 3T3 cells expressing trk proto-oncogene products indicated that only the mature form, gp140/sup proto-trk/, cross the plasma membrane, becoming exposed to the outside of the cell. These results indicate that the product of the human trk locus is a novel tyrosine kinase cell surface receptor for an as yet unknown ligand.
- Research Organization:
- Sections of Developmental Oncology and Immunochemistry, Basic Research Program, National Cancer Institute Frederick Cancer Research Facility, Frederick, MD (US); Dept. of Oncology, Free Univ. Hospital, 1007 MB Amsterdam (NL); Dept. of Molecular Biology, Squibb Institute for Medical Research, Princeton, NJ (US)
- OSTI ID:
- 5821692
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 9:1
- Country of Publication:
- United States
- Language:
- English
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GLYCOPROTEINS
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CARCINOMAS
ONCOGENES
MOLECULAR BIOLOGY
PHOSPHOTRANSFERASES
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CELL MEMBRANES
DNA SEQUENCING
GENE REPRESSORS
ONCOGENIC TRANSFORMATIONS
RECEPTORS
TYROSINE
AMINO ACIDS
BODY
CARBOXYLIC ACIDS
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CELL TRANSFORMATIONS
CHEMISTRY
DIGESTIVE SYSTEM
DISEASES
ENZYMES
GASTROINTESTINAL TRACT
HYDROXY ACIDS
INTESTINES
MAPPING
MEMBRANE PROTEINS
MEMBRANES
NEOPLASMS
NUCLEOPROTEINS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
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550400* - Genetics
550200 - Biochemistry