Role of A kinase anchor proteins in the tissue-specific regulation of lipoprotein lipase

Gouri Ranganathan, Irina Pokrovskaya, Subramanian Ranganathan, Philip A. Kern

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Activation of protein kinase A by catecholamines inhibits lipoprotein lipase (LPL) activity through the elaboration of an RNA binding complex, which inhibits LPL translation by binding to the 3′-untranslated region of the LPL mRNA. To better define this process, we reconstituted the inhibitory RNA binding complex in vitro and demonstrated that the K homology (KH) domain of A kinase anchor protein (AKAP) 121/149 plays a vital role in the inhibition of LPL translation. Inhibition of LPL translation occurred in vitro only when the Cα subunit, R subunit, and AKAP 149 were present. Using different glutathione-S-transferase fusion proteins of AKAP 149, sequences containing the KH domain were required for inhibition of LPL translation, and the inhibition of AKAP 121 expression in 3T3-F442A adipocytes with short interfering RNA resulted in loss of epinephrine-mediated translation inhibition. After epinephrine injection into mice, LPL activity was inhibited in white adipose tissue but not in brown adipose tissue (BAT) or muscle. LPL activity and synthetic rate were inhibited in vitro by the addition of epinephrine to 3T3-F442A adipocytes, but there was no effect in L6 muscle cells and cultures of brown adipocytes. Corresponding with these differences in LPL translation, AKAP 121 protein and mRNA were abundantly expressed in mouse white adipose tissue, but was either very low or undetectable in BAT and muscle. Thus, AKAP 121/149 contains a KH region that is essential to the translation inhibition of LPL in response to epinephrine. BAT and muscle do not express significant AKAP 121/149, and this likely explains some of the tissue-specific differences in LPL regulation.

Original languageEnglish
Pages (from-to)2527-2534
Number of pages8
JournalMolecular Endocrinology
Issue number10
StatePublished - Oct 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology


Dive into the research topics of 'Role of A kinase anchor proteins in the tissue-specific regulation of lipoprotein lipase'. Together they form a unique fingerprint.

Cite this