Molecular and Cellular Biology · 2009 · 70 citations · 56 references
Life SciencesCell BiologyMolecular BiologyCell SignalingCytoskeletonMolecular Cell BiologyCytoskeletal Associated ProteinsMicrotubule-associated ProteinsMotor ProteinsProtein Kinase CascadesProtein PhosphorylationSmall Gtpase Signaling14-3-3 Protein Binding RegulationExchange Proteins Activated By Cyclic Adenosine MonophosphateExchange Proteins Directly Activated By Cyclic Adenosine MonophosphatePhosphorylation CascadesPhosphorylation-dependent ActivationPhosphorylation-dependent RegulationProtein Phosphorylation SignalingRho Family Gtpases
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.
56
p115 RhoGEF, a GTPase Activating Protein for Gα <sub>12</sub> and Gα <sub>13</sub>
Tohru Kozasa, Xuejun Jiang, Matthew J. Hart et al. · Science · 1998 · 850 citations
Human Sos1: a Guanine Nucleotide Exchange Factor for Ras that Binds to GRB2
Pierre Teilhard de Chardin, Jacques Camonis, Nicholas W. Gale et al. · Science · 1993 · 800 citations