Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia.
Because mutations in receptor tyrosine kinases may contribute to cellular transformation, studies were undertaken to examine c-kit in human leukemia. Isoforms of c-kit have been characterized in the human megakaryoblastic leukemia cell line M-07. Deletion of the four amino acids Gly-Asn-Asn-Lys in the extracellular domain represents an alternatively spliced isoform that has been shown by others, in mice, to be associated with constitutive receptor autophosphorylation (Reith et al, EMBO J 10:2451, 1991). Additional isoforms differ in the inclusion or exclusion of a serine residue in the interkinase domain, a region that contains the binding site for phosphatidylinositol 3-kinase. By RNase protection analysis, we have shown coexpression of the Gly-Asn-Asn-Lys+ and Gly-Asn-Asn-Lys- isoforms, with dominance of the Gly-Asn-Asn-Lys- transcript, in normal human bone marrow, normal melanocytes, a range of tumor cell lines, and the blasts of 23 patients with acute myeloid leukemia. Analysis of transcripts for the Ser+ and Ser- isoforms also showed coexpression in all normal and leukemic cells examined. The ratios of isoform expression for both the Gly-Asn-Asn-Lys and Ser variants were relatively constant, providing no evidence in the tumors examined that upregulation of one isoform contributes to the neoplastic process.
Crosier
P S
PS
Department of Molecular Medicine, School of Medicine, University of Auckland, New Zealand.
Ricciardi
S T
ST
Hall
L R
LR
Vitas
M R
MR
Clark
S C
SC
Crosier
K E
KE
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D006801:Humans; D007527:Isoenzymes / Q000032:analysis* / Q000502:physiology; D007938:Leukemia / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit; D011956:Receptors, Cell Surface / Q000032:analysis*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D004247:DNA; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit