FRIP, a hematopoietic cell-specific rasGAP-interacting protein phosphorylated in response to cytokine stimulation

Immunity. 1998 Jul;9(1):13-24. doi: 10.1016/s1074-7613(00)80584-1.

Abstract

The human IL-4 receptor contains a sequence (the 14R motif) centered on Y497 that, when phosphorylated, interacts with phosphotyrosine-binding (PTB) domain proteins. Here, we describe a PTB domain protein, FRIP, that is phosphorylated in response to cytokine stimulation. FRIP is related to the rasGAP-associated protein p62dok and is bound by the N-terminal SH2 domain of rasGAP. The frip gene maps to the hairless (hr) locus on mouse chromosome 14. hr/hr mice exhibit lymphadenopathy, and their lymph node T cells proliferate more vigorously to anti-CD3 with IL-4 or IL-2 stimulation than +/hr T cells. FRIP expression is significantly reduced in T cells from hr/hr mice. FRIP may negatively regulate proliferation by acting as an adapter molecule between rasGAP and receptor complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Line
  • Cell Line, Transformed
  • Cells, Cultured
  • Chromosome Mapping
  • DNA, Complementary
  • DNA-Binding Proteins*
  • Female
  • GTPase-Activating Proteins
  • Humans
  • Interleukin-2 / physiology
  • Interleukin-3 / physiology
  • Interleukin-4 / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Phosphoproteins / chemistry
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Messenger
  • RNA-Binding Proteins*
  • Receptors, Interleukin-4 / genetics
  • Receptors, Interleukin-4 / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Transcription Factors*

Substances

  • DNA, Complementary
  • DNA-Binding Proteins
  • DOK1 protein, human
  • Dok1 protein, mouse
  • GAP-associated protein p62
  • GTPase-Activating Proteins
  • HR protein, human
  • Interleukin-2
  • Interleukin-3
  • Phosphoproteins
  • Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, Interleukin-4
  • Recombinant Fusion Proteins
  • Transcription Factors
  • hr protein, mouse
  • Interleukin-4
  • Phosphotyrosine

Associated data

  • GENBANK/AF030627