title: Interleukin-3 induces the phosphorylation of a distinct fraction of bcl-2.
abstract: Bcl-2-related proteins (i.e. Bcl-2 and Bax) regulate the effector stage of apoptosis and can modulate the entry of quiescent cells into the cell cycle. Phosphorylation of Bcl-2 is presumed to modify its apoptosis-inhibitory function. By utilizing an interleukin-3 (IL-3)-dependent hematopoietic cell line, we examined the structural requirements of Bcl-2 phosphorylation and the correlation of this post-translational modification with its function. In the presence of IL-3, constitutively expressed Bcl-2 was phosphorylated on serine residue(s), and phosphorylated Bcl-2 lost its capacity to heterodimerize with Bax. Whereas the majority of Bcl-2 resided in mitochondria, phosphorylation only affected a minor pool of total Bcl-2 that selectively partitioned into a soluble fraction. Cytosolic targeting of Bcl-2 greatly increased its ratio of phosphorylation. Bcl-2 phosphorylation was reduced during IL-3 deprivation, and its phosphorylation was also delayed after transient cytokine deprivation. This pattern of phosphorylation temporally correlated with the accelerated exit and delayed reentry of Bcl-2-expressing cells into the cell cycle upon transient IL-3 deprivation and subsequent cytokine restimulation. Thus, IL-3-induced phosphorylation of a distinct pool of Bcl-2 may contribute to the inactivation of its antiproliferative function.
authors.affiliation: Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Poommipanit
authors.forename: B
authors.initials: B
authors.lastname: Chen
authors.forename: Z N
authors.initials: ZN
authors.lastname: Oltvai
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D019281:Dimerization; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation; D011487:Protein Conformation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D007377:Interleukin-3; D019253:Proto-Oncogene Proteins c-bcl-2