The trk oncogene abrogates growth factor requirements and transforms hematopoietic cells.
Oncogenes may cause transformation by altering the requirements of cells for growth factors which normally regulate growth. This type of transformation is particularly evident in the ability of oncogenes of the tyrosine protein kinase gene family to abrogate the requirement of hematopoietic cells for growth factors such as interleukin-3 (IL-3). We have used this property to study the effect of the human trk oncogene on hematopoietic cells. This oncogene was generated by a genetic rearrangement that fused a non-muscle tropomyosin gene to a tyrosine protein kinase with structural features characteristic of growth factor receptors. The results presented here demonstrate that a replication-defective murine retrovirus expressing the human trk oncogene can abrogate the growth factor requirements of hematopoietic cells through a non-autocrine mechanism. In these trk-transformed cells, many of the cellular proteins which are phosphorylated on tyrosine residues following IL-3 stimulation are constitutively phosphorylated, with the notable exception of a 140 kDa membrane, IL-3-binding protein. The 140 kDa protein becomes phosphorylated only following stimulation with IL-3 in these trk oncogene-transformed hematopoietic cells.
Katzav
S
S
Developmental Oncology Section, NCI-Frederick Cancer Research Facility, Maryland 21701.
Martin-Zanca
D
D
Barbacid
M
M
Hedge
A M
AM
Isfort
R
R
Ihle
J N
JN
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006413:Hematopoietic System / Q000473:pathology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D011519:Proto-Oncogenes; D012190:Retroviridae / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism
D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases