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.
Nelms
K
K
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Snow
A L
AL
Hu-Li
J
J
Paul
W E
WE
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