Molecular cloning and chromosomal localisation of the human homologue of a receptor related to tyrosine kinases (RYK).
A cDNA encoding the human homologue of mouse RYK (related to receptor tyrosine kinases) has been cloned from an interleukin 1 (IL-1)-stimulated human hepatoma cDNA library by cross-species hybridization using the mouse RYK cDNA as a probe. The sequence of the 3067-bp cDNA clone encoding human RYK predicts a transmembrane protein with a cytoplasmic domain that contains the consensus sequences (subdomains I-XI) of the protein tyrosine kinase (PTK) family. The highly conserved motif -D-F-G- (subdomain VII) of the catalytic domain of other receptor-type tyrosine kinases is altered to -D-N-A- in human RYK. In addition, a number of other changes were found in the ATP binding site (subdomains I and II) and the motif [-I-H-R-D-L-A-A-R-N-] found in subdomain VI. Comparison of the human and mouse RYK sequences shows a 92% conservation at the nucleotide level and 97% at the amino acid level. There was no significant homology between the extracellular domain of RYK and the other families of receptor tyrosine kinases described to date. RYK therefore appears to define a new subclass of receptor-type tyrosine kinases whose structure has remained highly conserved across species.
Ludwig Institute for Cancer Research, Royal Melbourne Hospital Parkville, Victoria, Australia.
S A
SA
Stacker
C M
CM
Hovens
A
A
Vitali
M A
MA
Pritchard
E
E
Baker
G R
GR
Sutherland
A F
AF
Wilks
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; C080836:RYK protein, human; D020794:Receptor Protein-Tyrosine Kinases