v-raf suppresses apoptosis and promotes growth of interleukin-3-dependent myeloid cells.
Interleukin-3 (IL-3) is required for the proliferation, survival and differentiation of myeloid progenitors. In the absence of IL-3, murine myeloid 32D.3 cells accumulate in the G1 phase of the cell cycle and subsequently undergo programmed cell death, or apoptosis. Here we demonstrate that enforced expression of the v-raf oncogene suppresses apoptosis of myeloid 32D.3 cells following the withdrawal of IL-3. Surprisingly, steady state levels of Bcl-2, an oncogene known to suppress apoptosis, were not dependent upon IL-3 in 32D.3 cells and its levels were not augmented in v-raf clones. This suggests that ability of v-raf to suppress apoptosis in the absence of ligand is either Bcl-2 independent or that v-raf kinase promotes Bcl-2 function. v-raf also promoted growth of these cells in the presence of IL-3. v-raf clones proliferated at an increased rate due to a shortened G1 phase and had decreased requirements for IL-3 for growth. Therefore, transformation of myeloid cells by v-raf involves signaling pathways which promote both cell cycle progression and cell survival.
Cleveland
J L
JL
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Troppmair
J
J
Packham
G
G
Askew
D S
DS
Lloyd
P
P
González-Garcia
M
M
Nuñez
G
G
Ihle
J N
JN
Rapp
U R
UR
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells; D002455:Cell Division; D002478:Cells, Cultured; D016259:Genes, myc; D007377:Interleukin-3 / Q000502:physiology*; D051379:Mice; D027384:Oncogene Proteins v-raf; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015682:Retroviridae Proteins, Oncogenic; D027384:Oncogene Proteins v-raf