Phosphotyrosine-containing lactate dehydrogenase is restricted to the nuclei of PC12 pheochromocytoma cells.
There are five lactate dehydrogenase (LDH) isoenzymes, composed of various combinations of two types of subunits. LDH-5, which contains only the LDH A subunit, is known to be present in both the cytoplasm and the nucleus, to act as a single-stranded DNA-binding protein possibly functioning in transcription and/or replication, and to undergo phosphorylation of tyrosine 238 in approximately 1% of the enzyme after cell transformation by certain tumor viruses. We have characterized LDH from wild-type PC12 pheochromocytoma cells and from a PC12 variant (MPT1) that exhibits altered lactate metabolism and altered expression of multiple genes. Wild-type and MPT1 cells contain different proportions of LDH isoenzymes, with LDH-5 being more predominant in wild-type cells than in the variant. A small fraction of LDH from PC12 cells contains phosphotyrosine. Approximately 99% of the total LDH activity is located in the cytoplasm, but all of the phosphotyrosine-containing LDH is located in the nucleus. Furthermore, essentially all of the nuclear LDH contains phosphotyrosine. These results suggest that tyrosine phosphorylation can affect its role in the nucleus.
Zhong
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XH
Department of Biological Chemistry, School of Medicine, University of California, Los Angeles 90024.
Howard
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BD
D000310:Adrenal Gland Neoplasms / Q000201:enzymology; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology*; D002846:Chromatography, Affinity; D003593:Cytoplasm / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000302:isolation & purification* / Q000378:metabolism; D010673:Pheochromocytoma / Q000201:enzymology; D010710:Phosphates / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D019000:Phosphotyrosine; D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis; D014638:Vanadates / Q000494:pharmacology
D004268:DNA-Binding Proteins; D007527:Isoenzymes; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D019000:Phosphotyrosine; D014638:Vanadates; D014443:Tyrosine; D007770:L-Lactate Dehydrogenase