Modulation of Rho guanine exchange factor Lfc activity by protein kinase A-mediated phosphorylation

David Meiri, Melissa A. Greeve, Andrea Brunet, Dina Finan, Clark Wells, Jose LaRose, Robert Rottapel

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Lfc is a guanine nucleotide exchange factor (GEF) for Rho that demonstrates an unusual ability to associate with microtubules. While several phosphorylated residues have been detected in the Lfc polypeptide, the mechanism(s) by which phosphorylation regulates the exchange activity of Lfc remains unclear. We confirm that Lfc is a phosphorylated protein and demonstrate that 14-3-3 interacts directly and in a phosphorylation-dependent manner with Lfc. We identify AKAP121 as an Lfc-binding protein and show that Lfc is phosphorylated in an AKAP-dependent manner by protein kinase A (PKA). Forskolin treatment induced 14-3-3 binding to Lfc and suppressed the exchange activity of wild-type Lfc on RhoA. Importantly, a mutant of Lfc that is unable to associate with 14-3-3 proteins was resistant to inhibition by forskolin. Tctex-1, a dynein motor light chain, binds to Lfc in a competitive manner with 14-3-3.

Original languageEnglish (US)
Pages (from-to)5963-5973
Number of pages11
JournalMolecular and Cellular Biology
Volume29
Issue number21
DOIs
StatePublished - Nov 2009
Externally publishedYes

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14-3-3 Proteins
Guanine
Colforsin
Cyclic AMP-Dependent Protein Kinases
Rho Guanine Nucleotide Exchange Factors
Phosphorylation
Dyneins
Microtubules
Carrier Proteins
Peptides

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Modulation of Rho guanine exchange factor Lfc activity by protein kinase A-mediated phosphorylation. / Meiri, David; Greeve, Melissa A.; Brunet, Andrea; Finan, Dina; Wells, Clark; LaRose, Jose; Rottapel, Robert.

In: Molecular and Cellular Biology, Vol. 29, No. 21, 11.2009, p. 5963-5973.

Research output: Contribution to journalArticle

Meiri, David ; Greeve, Melissa A. ; Brunet, Andrea ; Finan, Dina ; Wells, Clark ; LaRose, Jose ; Rottapel, Robert. / Modulation of Rho guanine exchange factor Lfc activity by protein kinase A-mediated phosphorylation. In: Molecular and Cellular Biology. 2009 ; Vol. 29, No. 21. pp. 5963-5973.
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