Interleukin-3 signals through multiple isoforms of Stat5.
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.
Azam
M
M
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Erdjument-Bromage
H
H
Kreider
B L
BL
Xia
M
M
Quelle
F
F
Basu
R
R
Saris
C
C
Tempst
P
P
Ihle
J N
JN
Schindler
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D015723:Gene Library; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D008894:Milk Proteins; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D019000:Phosphotyrosine; D050799:STAT5 Transcription Factor; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D004268:DNA-Binding Proteins; D007377:Interleukin-3; D008894:Milk Proteins; D015345:Oligonucleotide Probes; D010446:Peptide Fragments; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D019000:Phosphotyrosine; D014443:Tyrosine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor