Disease relevance of PKM2

• In five of eight human colorectal cancers investigated, PGK1 and PKM2 mRNA levels were increased in comparison to the corresponding normal tissues, while HIF-1alpha mRNA levels were not significantly changed [1].
• Life-threatening nonspherocytic hemolytic anemia in a patient with a null mutation in the PKLR gene and no compensatory PKM gene expression [2].
• In human choriocarcinoma JEG-3 and monkey COS-1 cells, the cytosolic thyroid hormone binding protein is a monomer of the tetrameric pyruvate kinase, subtype M2, which does not bind T3 [3].
• A novel protein kinase, Mx-interacting protein kinase (PKM), has been identified in a yeast two-hybrid screen for interaction partners of human MxA, an interferon-induced GTPase with antiviral activity against several RNA viruses [4].
• Here we present evidence that 3,4,3',4'-tetrachlorobiphenyl (TCB) (PCB77), a PCB with high toxicity and significant bioaccumulation, can act as an estrogen with actions mediated through the estrogen receptor [5].

Psychiatry related information on PKM2

• We examined the potential involvement of such aberrant phosphorylation in certain aspects of the neurodegeneration accompanying Alzheimer's disease by microinjecting PKC and PKM, along with a rhodamine-conjugated dextran tracer, into undifferentiated NB2a/d1 mouse neuroblastoma cells [6].
• Those concerning MS, PD/PKM, and dementia included a small number of disease categories [7].
• This article describes the development and preliminary psychometric properties of the Transition Competence Battery for Deaf Adolescents and Young Adults (TCB) [8].

High impact information on PKM2

• Rounding-up on the TCB Cytokinesis series [9].
• Interest in apoptosis is currently growing rapidly, and previous articles in this series in TCB have described a number of recent advances in the field [10].
• The role of various members of the kinesin superfamily in chromosome segregation and spindle morphogenesis was described in TCB last year in parts of a series on cytoplasmic motor proteins [11].
• In addition, osteoclast-conditioned medium had no collagenolytic activity, and exogenous TCA and TCB fragments were not degraded by osteoclasts [12].
• At the physiological T3 concentration, lowering the glucose concentration led to an increase in the cellular concentration of the cytosolic thyroid hormone binding protein [3].

Biological context of PKM2

• The active site of hPKM2 is in a partially closed conformation most likely resulting from a ligand-induced domain closure promoted by the binding of FBP [13].
• In most cancer cells, hPKM2 is once again expressed to promote tumor cell proliferation [13].
• Gene dosage studies yielded results consistent with the assignment of the locus for pyruvate kinase (PK3) to chromosome 15 [14].
• PK3: a new chromosome enzyme marker for gene dosage studies in chromosome 15 imbalance [14].
• The exon-intron structure of the human PKM gene is identical to that of the rat gene, and the introns of both genes interrupt the exons at the same points [15].

Anatomical context of PKM2

• Also THBP expression was found in various tumors whereas in normal tissues, its expression is restricted to the testis and, at lower levels, in ovary, liver, and spleen [16].
• Human pyruvate kinase isozyme M2 (hPKM2) is expressed in early fetal tissues and is progressively replaced by the other three isozymes, M1, R, and L, immediately after birth [13].
• The molecular mechanisms for nongenomic actions are incompletely understood; relevant binding sites and signal transduction pathways have been described for hormone actions on plasma membrane Ca(2+)-ATPase activity, and PKM2 monomer is known to bind T3 and, as a result, prevent activation of the kinase via tetramer formation [17].
• Synteny of the loci for beta2-microglobulin and PKM2 in man-mouse somatic cell hybrid subclones [18].
• Immunofluorescence staining and confocal scanning experiments showed that PanK4 could transiently co-express with Pkm2 in the cytoplasm of HeLa cell and HEK293T cell [19].

Associations of PKM2 with chemical compounds

• Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase [20].
• PKR from these people was thermounstable and M2-like PK was identical to PKM2 for immunologic reactivity and KO, 5s for phosphoenolpyruvate [21].
• However, PKM2 was dissociated into monomer within minutes after cells were deprived of glucose [22].
• Analysis of the molecular size indicated that the activation of p58-M2, by Fru-1,6-P2 resulted in the association of the monomeric p58-M2 to the tetrameric PKM2. p58-M2 bound to 3,3',5-triiodo-L-thyronine (T3) (Ka = 1.7 x 10(7) M-1) and exhibited analogue specificity, whereas PKM2 did not bind thyroid hormone [23].
• A single phosphorylation of PK3 by cyclic AMP-dependent protein kinase diminished its assembly-accelerating property [24].

Other interactions of PKM2

• The following syntenic groups were observed but could not be localized: GUK1-FH and MPI-PKM2 [25].
• RESULTS: The correlation between Tac trough levels and Tac-AUCs were r = .95 PK1; r = .82, PK2; and r = .88, PK3 [26].

Analytical, diagnostic and therapeutic context of PKM2

• The collagenase found in lavage fluid in IPF cleaved lung collagen into collagenase-specific TCA and TCB fragments [27].
• The first of two biochemical analyses, Western blot analysis, demonstrated that eggs activated with calcium ionophore contained PKC in the detergent-soluble fraction and PKM in the sheet enriched fraction [28].
• CONCLUSION: Despite modern drug therapy, PKM continues to confer a sharply increased mortality on unselected patients followed for several years [29].
• The cases with PKM had an overall mortality odds ratio of 2.5 (95% CI: 2.4, 2.6) compared with the control group [29].
• The ability of the constitutively active fragment of protein kinase C (PKM) to modulate N-methyl-D-aspartate (NMDA)-activated currents in cultured mouse hippocampal neurons and acutely isolated CA1 hippocampal neurons from postnatal rats was studied using patch-clamp techniques [30].

References