Phosphotyrosine-Containing Lactate Dehydrogenase Is Restricted to the Nuclei of PC12 Pheochromocytoma Cells

Abstract

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.

PIM kinases phosphorylate lactate dehydrogenase A at serine 161 and suppress its nuclear ubiquitination

“…However, the majority of LDHA proteins and their activities are located in cytosolic fractions, which is in agreement with previous observations, e.g. from PC12 cells [43]. So far, there are at least two independent reports on the phosphorylation of LDHA at both serine and tyrosine residues [42,43].…”

“…Despite several reports on the presence of LDHA in the nucleus [23,25,28,[42][43][44], it has conventionally been depicted as a cytosolic enzyme. Notably, immunohistochemistry stainings have revealed both cytoplasmic and nuclear LDHA expression in lung cancer cells [25,28].…”

“…from PC12 cells [43]. So far, there are at least two independent reports on the phosphorylation of LDHA at both serine and tyrosine residues [42,43]. While the functional consequences of tyrosine phosphorylation of LDHA have been actively explored [33,34], studies on serine phosphorylation are lagging behind.…”

Antinociceptive Effects of Aaptamine, a Sponge Component, on Peripheral Neuropathy in Rats

“…Neuropathic pain is also accompanied by overexpression of HIF1α by ROS, hypoxia, and ischemia stimulation [ 68 , 69 , 70 ]. Previous studies have demonstrated that HIF1α signaling and ROS accumulation would regulate neuronal LDHA translocation [ 19 , 71 , 72 , 73 ]. Moreover, LDHA, as a transcription factor, can regulate VEGF gene expression and promote angiogenesis [ 74 ].…”