Activation/division of lymphocytes results in increased levels of cytoplasmic activation/proliferation-associated protein-1: prototype of a new family of proteins.
We purified from activated T lymphocytes a novel, highly conserved, 116-kDa, intracellular protein that occurred at high levels in the large, dividing cells of the thymus, was up-regulated when resting T or B lymphocytes or hemopoietic progenitors were activated, and was down-regulated when a monocytic leukemia, M1, was induced to differentiate. Expression of the protein was highest in the thymus and spleen and lowest in tissues with a low proportion of dividing cells such as kidney or muscle, although expression was high in the brain. The protein was localized to the cytosol and was phosphorylated, which is consistent with a previous report that the Xenopus laevis ortholog was phosphorylated by a mitotically activated kinase (1 ). The cDNA was previously mischaracterized as encoding p137, a 137-kDa GPI-linked membrane protein (2 ). We propose that the authentic protein encoded by this cDNA be called cytoplasmic activation/proliferation-associated protein-1 (caprin-1), and show that it is the prototype of a novel family of proteins characterized by two novel protein domains, termed homology regions-1 and -2 (HR-1, HR-2). Although we have found evidence for caprins only in urochordates and vertebrates, two insect proteins exhibit well-conserved HR-1 domains. The HR-1 and HR-2 domains have no known function, although the HR-1 of caprin-1 appeared necessary for formation of multimeric complexes of caprin-1. Overexpression of a fusion protein of enhanced green fluorescent protein and caprin-1 induced a specific, dose-dependent suppression of the proliferation of NIH-3T3 cells, consistent with the notion that caprin-1 plays a role in cellular activation or proliferation.
Grill
Brock
B
The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Wilson
Gary M
GM
Zhang
Kai-Xin
KX
Wang
Bin
B
Doyonnas
Regis
R
Quadroni
Manfredo
M
Schrader
John W
JW
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D017124:Conserved Sequence; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006131:Growth Inhibitors / Q000737:chemistry; D006133:Growth Substances / Q000172:deficiency; D006410:Hematopoiesis; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry; D008164:Luminescent Proteins / Q000235:genetics; D008213:Lymphocyte Activation; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D008970:Molecular Weight; D041681:NIH 3T3 Cells; D009928:Organ Specificity / Q000276:immunology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology; D029867:Xenopus Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics
C486569:CAPRIN1 protein, Xenopus; C486562:CAPRIN1 protein, human; C486571:CAPRIN2 protein, human; C486565:Caprin1 protein, mouse; D018797:Cell Cycle Proteins; D006131:Growth Inhibitors; D006133:Growth Substances; D019476:Insect Proteins; D008164:Luminescent Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D029867:Xenopus Proteins; D049452:Green Fluorescent Proteins