PTPROt: an alternatively spliced and developmentally regulated B-lymphoid phosphatase that promotes G0/G1 arrest.
Protein tyrosine phosphatases (PTP) regulate the proliferation, differentiation, and viability of lymphocytes by modulating their signaling pathways. By using the differential display assay, we have cloned a putative receptor-type PTP, which is predominantly expressed in B-lymphoid tissues (lymph nodes and spleen). This PTP, termed PTPROt (truncated), is a tissue-specific alternatively-spliced form of a human epithelial PTP, PTPRO (PTPU2/GLEPP1). Whereas the epithelial PTPRO includes an approximately 800-amino acid extracellular domain, the major (3 kb) PTPROt cDNA predicts a unique 5' untranslated region and truncated (8 amino acids) extracellular domain with a conserved transmembrane region and single catalytic domain. PTPROt cDNAs encode functional approximately 47-kD and approximately 43-kD PTPs, which are most abundant in normal naive quiescent B cells and decreased or absent in germinal center B cells and germinal center-derived diffuse large B-cell lymphomas. Because PTPROt was predominantly expressed in naive quiescent B cells, the enzyme's effects on cell-cycle progression were examined. When multiple stable PTPROt sense, antisense, and vector only B-cell transfectants were grown in reduced serum and synchronized with nocodazole, PTPROt sense clones exhibited markedly increased G0/G1 arrest. Taken together, these data implicate PTPROt in the growth control of specific B-cell subpopulations.
Aguiar
R C
RC
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
Yakushijin
Y
Y
Kharbanda
S
S
Tiwari
S
S
Freeman
G J
GJ
Shipp
M A
MA
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology*; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary; D016193:G1 Phase; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007438:Introns; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000494:pharmacology; D014066:Palatine Tonsil / Q000276:immunology; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D017384:Sequence Deletion; D013154:Spleen / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D017027:Protein Tyrosine Phosphatases; D015739:Nocodazole