Gene interactions and pathways from curated databases and text-mining
J Biol Chem 1999, PMID: 10358045

STAT protein recruitment and activation in c-Kit deletion mutants.

Brizzi, M F; Dentelli, P; Rosso, A; Yarden, Y; Pegoraro, L

Stem cell factor (SCF) and its tyrosine kinase receptor, c-Kit, play a crucial role in regulating migration and proliferation of melanoblasts, germ cells, and hemopoietic cell progenitors by activating a number of intracellular signaling molecules. Here we report that SCF stimulation of myeloid cells or fibroblasts ectopically expressing c-Kit induces physical association with and tyrosine phosphorylation of three signal transducers and activators of transcription (STATs) as follows: STAT1alpha, STAT5A, and STAT5B. Other STAT proteins are not recruited upon SCF stimulation. Recruitment of STATs leads to their dimerization, nuclear translocation, and binding to specific promoter-responsive elements. Whereas STAT1alpha, possibly in the form of homodimers, binds to the sis-inducible DNA element, STAT5 proteins, either as STAT5A/STAT5B or STAT5/STAT1alpha heterodimers, bind to the prolactin-inducible element of the beta-casein promoter. The tyrosine kinase activity of Kit appears essential for STAT activation since a kinase-defective mutant lacking a kinase insert domain was inactive in STAT signaling. However, another mutant that lacked the carboxyl-terminal region retained STAT1alpha activation and nuclear translocation but was unable to fully activate STAT5 proteins, although it mediated their transient phosphorylation. These results indicate that different intracellular domains of c-Kit are involved in activation of the various STAT proteins.

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Text Mining Data

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Manually curated Databases

  • IRef Hprd Interaction: STAT5B — KIT (in vivo)
  • IRef Hprd Interaction: STAT5A — STAT1 (in vitro)
  • IRef Hprd Interaction: STAT5A — STAT1 (in vivo)
  • IRef Hprd Interaction: STAT1 — STAT5B (in vivo)
  • IRef Hprd Interaction: STAT1 — STAT5B (in vitro)
  • IRef Hprd Interaction: STAT5A — KIT (in vivo)
  • Reactome Reaction: LYN → STAT1 (indirect_complex)
  • Reactome Reaction: STAT5A → KITLG (reaction)
  • Reactome Reaction: JAK2 → STAT3 (indirect_complex)
  • Reactome Reaction: STAT5B → KITLG (indirect_complex)
  • Reactome Reaction: YES1 → STAT1 (reaction)
  • Reactome Reaction: STAT5B → KITLG (reaction)
  • Reactome Reaction: STAT5A → YES1 (indirect_complex)
  • Reactome Reaction: KITLG → STAT1 (indirect_complex)
  • Reactome Reaction: LCK → STAT1 (reaction)
  • Reactome Reaction: KIT → STAT5A (reaction)
  • Reactome Reaction: JAK2 → KIT (indirect_complex)
  • Reactome Reaction: STAT1 → KITLG (indirect_complex)
  • Reactome Reaction: SRC → STAT5B (indirect_complex)
  • Reactome Reaction: FYN → STAT5A (reaction)
  • Reactome Reaction: FYN → STAT1 (indirect_complex)
  • Reactome Reaction: JAK2 → STAT1 (reaction)
  • Reactome Reaction: LCK → STAT1 (indirect_complex)
  • Reactome Reaction: FYN → STAT5B (reaction)
  • Reactome Reaction: STAT5B → YES1 (indirect_complex)
  • Reactome Reaction: LCK → STAT5A (reaction)
  • Reactome Reaction: SRC → STAT5A (indirect_complex)
  • Reactome Reaction: LCK → STAT5B (indirect_complex)
  • Reactome Reaction: STAT5A → KITLG (indirect_complex)
  • Reactome Reaction: KITLG → STAT3 (reaction)
  • Reactome Reaction: KIT → STAT5B (reaction)
  • Reactome Reaction: LYN → STAT5A (reaction)
  • Reactome Reaction: JAK2 → LCK (indirect_complex)
  • Reactome Reaction: JAK2 → KITLG (indirect_complex)
  • Reactome Reaction: LCK → STAT3 (indirect_complex)
  • Reactome Reaction: KIT → STAT3 (indirect_complex)
  • Reactome Reaction: JAK2 → STAT5B (indirect_complex)
  • Reactome Reaction: STAT1 → KITLG (reaction)
  • Reactome Reaction: YES1 → STAT1 (indirect_complex)
  • Reactome Reaction: KIT → STAT1 (reaction)
  • Reactome Reaction: KIT → STAT5A (indirect_complex)
  • Reactome Reaction: FYN → STAT5A (indirect_complex)
  • Reactome Reaction: STAT5B → YES1 (reaction)
  • Reactome Reaction: LYN → STAT3 (reaction)
  • Reactome Reaction: KITLG → STAT1 (reaction)
  • Reactome Reaction: FYN → STAT5B (indirect_complex)
  • Reactome Reaction: STAT5A → YES1 (reaction)
  • Reactome Reaction: LYN → STAT1 (reaction)
  • Reactome Reaction: LCK → STAT3 (reaction)
  • Reactome Reaction: JAK2 → STAT5A (reaction)
  • Reactome Reaction: KIT → STAT1 (indirect_complex)
  • Reactome Reaction: SRC → STAT3 (indirect_complex)
  • Reactome Reaction: KIT → STAT5B (indirect_complex)
  • Reactome Reaction: FYN → JAK2 (indirect_complex)
  • Reactome Reaction: YES1 → STAT3 (reaction)
  • Reactome Reaction: JAK2 → STAT5B (reaction)
  • Reactome Reaction: LYN → STAT5A (indirect_complex)
  • Reactome Reaction: JAK2 → STAT1 (direct_complex)
  • Reactome Reaction: FYN → STAT3 (reaction)
  • Reactome Reaction: SRC → STAT1 (indirect_complex)
  • Reactome Reaction: SRC → STAT1 (reaction)
  • Reactome Reaction: SRC → STAT5B (reaction)
  • Reactome Reaction: LYN → STAT5B (indirect_complex)
  • Reactome Reaction: KITLG → STAT3 (indirect_complex)
  • Reactome Reaction: YES1 → STAT3 (indirect_complex)
  • Reactome Reaction: LCK → STAT5A (indirect_complex)
  • Reactome Reaction: SRC → STAT3 (reaction)
  • Reactome Reaction: SRC → STAT5A (reaction)
  • Reactome Reaction: JAK2 → STAT5B (direct_complex)
  • Reactome Reaction: LYN → STAT5B (reaction)
  • Reactome Reaction: JAK2 → STAT1 (indirect_complex)
  • Reactome Reaction: JAK2 → STAT5A (indirect_complex)
  • Reactome Reaction: JAK2 → LYN (indirect_complex)
  • Reactome Reaction: FYN → STAT3 (indirect_complex)
  • Reactome Reaction: STAT1 → YES1 (indirect_complex)
  • Reactome Reaction: JAK2 → SRC (indirect_complex)
  • Reactome Reaction: JAK2 → STAT3 (reaction)
  • Reactome Reaction: KIT → STAT3 (reaction)
  • Reactome Reaction: LCK → STAT5B (reaction)
  • Reactome Reaction: JAK2 → YES1 (indirect_complex)
  • Reactome Reaction: STAT1 → YES1 (reaction)
  • Reactome Reaction: JAK2 → STAT3 (direct_complex)
  • Reactome Reaction: FYN → STAT1 (reaction)
  • Reactome Reaction: LYN → STAT3 (indirect_complex)
  • Reactome Reaction: JAK2 → STAT5A (direct_complex)
In total, 41 gene pairs are associated to this article in curated databases