RGD Reference Report - Expression of an active LKB1 complex in cardiac myocytes results in decreased protein synthesis associated with phenylephrine-induced hypertrophy. - Rat Genome Database

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Expression of an active LKB1 complex in cardiac myocytes results in decreased protein synthesis associated with phenylephrine-induced hypertrophy.

Authors: Noga, AA  Soltys, CL  Barr, AJ  Kovacic, S  Lopaschuk, GD  Dyck, JR 
Citation: Noga AA, etal., Am J Physiol Heart Circ Physiol. 2007 Mar;292(3):H1460-9. Epub 2006 Nov 10.
RGD ID: 1601391
Pubmed: PMID:17098823   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.01133.2006   (Journal Full-text)

AMP-activated protein kinase (AMPK) is a major metabolic regulator in the cardiac myocyte. Recently, LKB1 was identified as a kinase that regulates AMPK. Using immunoblot analysis, we confirmed high expression of LKB1 in isolated rat cardiac myocytes but show that, under basal conditions, LKB1 is primarily localized to the nucleus, where it is inactive. We examined the role of LKB1 in cardiac myocytes, using adenoviruses that express LKB1, and its binding partners Ste20-related adaptor protein (STRADalpha) and MO25alpha. Infection of neonatal rat cardiac myocytes with all three adenoviruses substantially increased LKB1/STRADalpha/MO25alpha expression, LKB1 activity, and AMPKalpha phosphorylation at its activating phosphorylation site (threonine-172). Since activation of AMPK can inhibit hypertrophic growth and since LKB1 is upstream of AMPK, we hypothesized that expression of an active LKB1 complex would also inhibit protein synthesis associated with hypertrophic growth. Expression of the LKB1/STRADalpha/MO25alpha complex in neonatal rat cardiac myocytes inhibited the increase in protein synthesis observed in cells treated with phenylephrine (measured via [(3)H]phenylalanine incorporation). This was associated with a decreased phosphorylation of p70S6 kinase and its substrate S6 ribosomal protein, key regulators of protein synthesis. In addition, we show that the pathological cardiac hypertrophy in transgenic mice with cardiac-specific expression of activated calcineurin is associated with a significant decrease in LKB1 expression. Together, our data show that increased LKB1 activity in the cardiac myocyte can decrease hypertrophy-induced protein synthesis and suggest that LKB1 activation may be a method for the prevention of pathological cardiac hypertrophy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiomegaly  ISOStk11 (Mus musculus)1601391; 1601391protein:decreased expression:heartRGD 
Cardiomegaly  IEP 1601391protein:decreased expression:heartRGD 

Objects Annotated

Genes (Rattus norvegicus)
Stk11  (serine/threonine kinase 11)

Genes (Mus musculus)
Stk11  (serine/threonine kinase 11)

Genes (Homo sapiens)
STK11  (serine/threonine kinase 11)


Additional Information