CIS1 interacts with the Y532 of the prolactin receptor and suppresses prolactin-dependent STAT5 activation

Takaho Endo, Atsuo Sasaki, Mayu Minoguchi, Akiko Joo, Akihiko Yoshimura

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Prolactin (PRL) interacts with a single-chain prolactin-specific receptor of the cytokine receptor superfamily. PRL triggers the activation of JAK2 kinase, which phosphorylates the PRL receptor itself, and of STAT5, a member of the family of signal transducers and activators of transcription (STAT). We have shown that the STAT5-dependent immediate early gene, CIS1 (Cytokine-Inducible SH2 domain-containing protein-1), suppresses PRL-induced STAT5 activation in vitro as well as in transgenic mice. To facilitate the study of the interactions between CIS1 and the PRL receptor, we have developed the yeast tri-hybrid system, a modification of the yeast two-hybrid system. We expressed CIS1 fused to the DNA-binding domain and PRL receptor cytoplasmic domain fused to the transcription activation domain in the presence or absence of the tyrosine kinase domain of JAK2 in yeast. CIS1 bound to the PRL receptor cytoplasmic domain in a JAK2-dependent manner. Moreover, we determined that the phosphorylated Y532 of the murine PRL receptor is the binding site for CIS1. Interestingly, Y532 has been shown to be unnecessary for STAT5 activation, although CIS1 overexpression suppressed PRL-induced STAT5 activation. These data suggest that the suppression of STAT5 activation by CIS1 is not due to a simple competition with STAT5 but rather to a modification of the receptor by CIS1 binding.

Original languageEnglish
Pages (from-to)109-113
Number of pages5
JournalJournal of Biochemistry
Volume133
Issue number1
DOIs
Publication statusPublished - 2003 Jan 1
Externally publishedYes

Fingerprint

Prolactin Receptors
Prolactin
Chemical activation
Yeast
Transcription
Hybrid systems
Yeasts
Two-Hybrid System Techniques
Cytokine Receptors
Immediate-Early Genes
src Homology Domains
Transducers
Protein-Tyrosine Kinases
Transgenic Mice
Transcriptional Activation
Phosphotransferases
Genes
Binding Sites
Cytokines
DNA

Keywords

  • Cytokine
  • JAK kinase
  • Phosphorylation
  • SH2 domain
  • STAT5

ASJC Scopus subject areas

  • Biochemistry

Cite this

CIS1 interacts with the Y532 of the prolactin receptor and suppresses prolactin-dependent STAT5 activation. / Endo, Takaho; Sasaki, Atsuo; Minoguchi, Mayu; Joo, Akiko; Yoshimura, Akihiko.

In: Journal of Biochemistry, Vol. 133, No. 1, 01.01.2003, p. 109-113.

Research output: Contribution to journalArticle

Endo, Takaho ; Sasaki, Atsuo ; Minoguchi, Mayu ; Joo, Akiko ; Yoshimura, Akihiko. / CIS1 interacts with the Y532 of the prolactin receptor and suppresses prolactin-dependent STAT5 activation. In: Journal of Biochemistry. 2003 ; Vol. 133, No. 1. pp. 109-113.
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