Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the context of a general survey on genetic variation of isozyme-gene systems which function in the carbohydrate degradation and conversion, we detected a reciprocal relationship between genetic diversity at the hexokinase (HEK-A) and phosphoglucose isomerase (PGI-B) loci in Scots pine populations. Further studies on Norway spruce, Douglas-fir and Siberian stone pine revealed that this relationship appears to be a more general phenomenon in conifers such that increasing diversity at one locus is correlated with a decrease in diversity at the other locus. Since the two gene loci are not structurally linked but are encoding enzymes of two sucessive metabolic steps in the glucose conversion towards glycolysis, it is assumed that some sort of selection, especially during germination and early embryo development, may be the causal explanation. A metabolically-based model incorporating selective advantage and disadvantage of alternate two-locus genotypes at HEK-A/PGI-B was presented in order to elucidate the possible adaptive nature of this reciprocal relationship.
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PMID:A reciprocal relationship between the genetic diversity at two metabolically-linked isozyme loci in several conifer species. 1151 76

AMP-activated protein kinase (AMPK) has been identified as a regulator of gene transcription, increasing mitochondrial proteins of oxidative metabolism as well as hexokinase expression in skeletal muscle. In mice, muscle-specific knockout of LKB1, a component of the upstream kinase of AMPK, prevents contraction- and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR)-induced activation of AMPK in skeletal muscle, and the increase in hexokinase II protein that is normally observed with chronic AICAR activation of AMPK. Since previous reports show a cAMP response element in the promoter region of the hexokinase II gene, we hypothesized that the cAMP-response element (CRE) binding protein (CREB) family of transcription factors could be targets of AMPK. Using radioisotopic kinase assays, we found that recombinant and rat liver and muscle AMPK phosphorylated CREB1 at the same site as cAMP-dependent protein kinase (PKA). AMPK was also found to phosphorylate activating transcription factor 1 (ATF1), CRE modulator (CREM), and CREB-like 2 (CREBL2), but not ATF2. Treatment of HEK-293 cells stably transfected with a CREB-driven luciferase reporter with AICAR increased luciferase activity approximately threefold over a 24-h time course. This increase was blocked with compound C, an AMPK inhibitor. In addition, AICAR-induced activation of AMPK in incubated rat epitrochlearis muscles resulted in an increase in both phospho-acetyl-CoA carboxylase and phospho-CREB. We conclude that CREB and related proteins are direct downstream targets for AMPK and are therefore likely involved in mediating some effects of AMPK on expression of genes having a CRE in their promoters.
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PMID:AMP-activated protein kinase phosphorylates transcription factors of the CREB family. 1806 5