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Prolactin Stimulates Serine/Tyrosine Phosphorylation and Formation of Heterocomplexes of Multiple Stat5 Isoforms in Nb2 Lymphocytes

  1. Author:
    Kirken, R. A.
    Malabarba, M. G.
    Xu, J.
    Liu, X. W.
    Farrar, W. L.
    Hennighausen, L.
    Larner, A. C.
    Grimley, P. M.
    Rui, H.
  2. Author Address

    Rui H UNIFORMED SERV UNIV HLTH SCI SCH MED DEPT PATHOL BETHESDA, MD 20814 USA UNIFORMED SERV UNIV HLTH SCI SCH MED DEPT PATHOL BETHESDA, MD 20814 USA SCI APPLICAT INT CORP INTRAMURAL RES SUPPORT PROGRAM FREDERICK, MD USA NCI FREDERICK CANC RES & DEV CTR DIV BASIC SCI MOL IMMUNOREGULAT LAB FREDERICK, MD 21702 USA NIDDK BIOCHEM & METAB LAB NIH BETHESDA, MD 20892 USA US FDA CTR BIOL EVALUAT & RES DIV CYTOKINE BIOL BETHESDA, MD 20814 USA
    1. Year: 1997
  1. Journal: Journal of Biological Chemistry
    1. 272
    2. 22
    3. Pages: 14098-14103
  2. Type of Article: Article
  1. Abstract:

    Transcription factors of the Stat gene family are selectively activated by many hormones and cytokines. Stat5 originally was cloned as a prolactin-stimulated DNA-binding protein, but is also activated by non-lactogenic cytokines in many cell types. The recent identification of two distinct Stat5 genes, which encode a 94-kDa Stat5a and a 92-kDa Stat5b as well as several lower molecular weight isoforms, suggests additional complexity and combinatorial possibilities for transcriptional regulation. We now report a biochemical analysis of prolactin activation of Stat proteins in Nb2 lymphocytes, which was associated with: 1) rapid tyrosine phosphorylation of Stat5a, Stat5b, a COOH-terminally truncated 80-kDa Stat5 form, Stat1 alpha, and Stat3; 2) rapid and selective formation of Stat5a/b heterodimers, without involvement of Stat1 alpha or Stat3; 3) marked serine, but not threonine phosphorylation of Stat5a and Stat5b; and 4) the appearance of two qualitatively distinct Stat5 protein complexes, which discriminated between oligonucleotides corresponding to the prolactin response elements of the beta-casein and interferon regulatory factor-1 gene promoters. Collectively, our analyses showed that Stat5a and Stat5b respond similarly to prolactin receptor activation, but also suggested that the two genes have evolved unique properties that may contribute to the specificity of receptors that utilize Stat5 signaling proteins. [References: 44]

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