Expression of a novel form of Tec kinase in hematopoietic cells and mapping of the gene to chromosome 5 near Kit.
The Tec kinase was initially identified as a novel cytoplasmic protein tyrosine kinase that is preferentially expressed in the liver and is highly homologous to the Drosophila Dsrc28C src-related tyrosine kinase. In screening of interleukin 3 (IL-3)-dependent myeloid leukemia cells for protein tyrosine kinases, we observed that all cell lines examined expressed high levels of Tec transcripts. However, characterization of Tec cDNAs indicated that they differed significantly from the published sequence. Most strikingly, an insertion of 41 bp in the 5' region affects the initiation codon and results in replacing the published 13 amino acid amino-terminal sequences with 94 amino acids. Using polymerase chain reaction (PCR) analysis, only the form containing the insertion was detected in hematopoietic cells. In addition, we found an in-frame insertion of 66 bp that introduces an additional 22 amino acids into the SH3 domain. This insertion restores conserved SH3 sequences that are found in the src gene family and in the Dsrc28C gene. By PCR analysis, approximately equal levels of Tec transcripts containing the intact SH3 domain and containing the 22 amino acid deletion were found in hematopoietic cells. Lastly, by interspecies backcross analysis, we show that the Tec gene is tightly linked to the c-Kit gene on mouse chromosome 5.
Mano
H
H
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Mano
K
K
Tang
B
B
Koehler
M
M
Yi
T
T
Gilbert
D J
DJ
Jenkins
N A
NA
Copeland
N G
NG
Ihle
J N
JN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D005260:Female; D015681:Fusion Proteins, gag-onc / Q000235:genetics; D016391:Genes, src; D006413:Hematopoietic System / Q000201:enzymology*; D007377:Interleukin-3 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes
D015681:Fusion Proteins, gag-onc; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; C068415:v-fps oncogene protein, Fujinami sarcoma virus