Interleukin-3 signals through multiple isoforms of Stat5.

Abstract

The interleukin (IL)‐3 family of cytokines mediates its numerous effects on myeloid growth and maturation by binding a family of related receptors. It has been shown recently that IL‐3 induces the activation of two distinct cytoplasmic signal transducing factors (STFs) that are likely to mediate the induction of immediate early genes. In immature myeloid cells, IL‐3 activates STF‐IL‐3a, which comprises two tyrosine‐phosphorylated DNA binding proteins of 77 and 80 kDa. In mature myeloid cells, IL‐3 and granulocyte‐macrophage colony‐stimulating factor activate STF‐IL‐3b, which consists of a 94 and 96 kDa tyrosine‐phosphorylated DNA binding protein. Peptide sequence data obtained from the purified 77 and 80 kDa proteins (p77 and p80) indicate that they are closely related but are encoded by distinct genes. Both peptide and nucleotide sequence data demonstrate that these two proteins are the murine homologs of ovine mammary gland factor (MGF)/Stat5. The peptide data also indicate that p77 and p80 are phosphorylated on tyrosine 699, a position analogous to the tyrosine that is phosphorylated in Stat1 and Stat2 in response to interferon. Additionally, antiserum raised against bacterially expressed p77/p80 recognizes the 94 and 96 kDa protein components of STF‐IL‐3b, suggesting that these may be additional isoforms of Stat5. These studies indicate that the IL‐3 family of ligands is able to activate multiple isoforms of the signal transducing protein Stat5.

A MGF/STAT5 binding site is necessary in the distal enhancer for high prolactin induction of transfected rabbit αs1‐casein‐CAT gene transcription

“…It is possible that another form of the MGF/STAT5-1ike factor binds to the same F4 probe. Several forms of MGF/STAT5 have been identified in the mouse [4,5], in the early myeloid cell line FDC-P1 [23], in rats [6] or in humans [7]. Another explanation could be that the MGF/STAT5-1ike factor binds to the F4 probe in association with a second transcription factor, the nature of which is not elucidated.…”

IL-3 signaling and the role of Src kinases, JAKs and STATs: a covert liaison unveiled

“…However, the nature of STATs activated seem to depend on the cell type that is being studied rather than on the nature of JAK activated or the nature of STATs expressed in these cell lines, as all of them seemed to express these STATs Azam et al, 1995;Mui et al, 1996;Chaturvedi et al, 1997Chaturvedi et al, , 1998. The two isoforms of STAT5, STAT5a and STAT5b as well as STAT6 are activated by receptors for IL-3, GM-CSF and IL-5 Azam et al, 1995). IL-3 stimulation leads to activation of JAK2 and phosphorylation and activation of STAT5a (via tyrosine phosphorylation of Y694) and STAT5b (via tyrosine phosphorylation of Y699).…”

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

“…In addition, isoforms of STAT1, STAT3, STAT5A, STAT5B that lack the COOH terminus, a region highly variable among STAT members containing the transactivation domain, have been described. These isoforms arise through an alternative splicing mechanism or a speci®c protein processing and are thought to be natural dominant negative forms of STAT proteins (Schindler et al, 1992;Azam et al, 1995Azam et al, , 1997Caldenhoven et al, 1996;Kazansky et al, 1995;Meyer et al, 1998;Schaefer et al, 1997;Wang et al, 1996).…”