axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase.
Using a sensitive transfection-tumorigenicity assay, we have isolated a novel transforming gene from the DNA of two patients with chronic myelogenous leukemia. Sequence analysis indicates that the product of this gene, axl, is a receptor tyrosine kinase. Overexpression of axl cDNA in NIH 3T3 cells induces neoplastic transformation with the concomitant appearance of a 140-kDa axl tyrosine-phosphorylated protein. Expression of axl cDNA in the baculovirus system results in the expression of the appropriate recombinant protein that is recognized by antiphosphotyrosine antibodies, confirming that the axl protein is a tyrosine kinase. The juxtaposition of fibronectin type III and immunoglobulinlike repeats in the extracellular domain, as well as distinct amino acid sequences in the kinase domain, indicate that the axl protein represents a novel subclass of receptor tyrosine kinases.
O'Bryan
J P
JP
Curriculum in Genetics, Lineberger Cancer Research Center, University of North Carolina, Chapel Hill 27599.
Frye
R A
RA
Cogswell
P C
PC
Neubauer
A
A
Kitch
B
B
Prokop
C
C
Espinosa
R
R
Le Beau
M M
MM
Earp
H S
HS
Liu
E T
ET
D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003001:Cloning, Molecular; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured; D000094963:Axl Receptor Tyrosine Kinase
D005353:Fibronectins; D007136:Immunoglobulins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase