FRIP, a hematopoietic cell-specific rasGAP-interacting protein phosphorylated in response to cytokine stimulation.
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.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
K
K
Nelms
A L
AL
Snow
J
J
Hu-Li
W E
WE
Paul
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002874:Chromosome Mapping; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005260:Female; D020690:GTPase-Activating Proteins; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D007377:Interleukin-3 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C489560:DOK1 protein, human; C489561:Dok1 protein, mouse; C074561:GAP-associated protein p62; D020690:GTPase-Activating Proteins; C490267:HR protein, human; D007376:Interleukin-2; D007377:Interleukin-3; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C088661:hr protein, mouse; D015847:Interleukin-4; D019000:Phosphotyrosine