TY - JOUR T1 - 14-3-3 Proteins Regulate Protein Kinase A Activity to Modulate Growth Cone Turning Responses JF - The Journal of Neuroscience JO - J. Neurosci. SP - 14059 LP - 14067 DO - 10.1523/JNEUROSCI.3883-10.2010 VL - 30 IS - 42 AU - Christopher B. Kent AU - Tadayuki Shimada AU - Gino B. Ferraro AU - Brigitte Ritter AU - Patricia T. Yam AU - Peter S. McPherson AU - Frédéric Charron AU - Timothy E. Kennedy AU - Alyson E. Fournier Y1 - 2010/10/20 UR - http://www.jneurosci.org/content/30/42/14059.abstract N2 - Growth cones regulate the speed and direction of neuronal outgrowth during development and regeneration. How the growth cone spatially and temporally regulates signals from guidance cues is poorly understood. Through a proteomic analysis of purified growth cones we identified isoforms of the 14-3-3 family of adaptor proteins as major constituents of the growth cone. Disruption of 14-3-3 via the R18 antagonist or knockdown of individual 14-3-3 isoforms switches nerve growth factor- and myelin-associated glycoprotein-dependent repulsion to attraction in embryonic day 13 chick and postnatal day 5 rat DRG neurons. These effects are reminiscent of switching responses observed in response to elevated cAMP. Intriguingly, R18-dependent switching is blocked by inhibitors of protein kinase A (PKA), suggesting that 14-3-3 proteins regulate PKA. Consistently, 14-3-3 proteins interact with PKA and R18 activates PKA by dissociating its regulatory and catalytic subunits. Thus, 14-3-3 heterodimers regulate the PKA holoenzyme and this activity plays a critical role in modulating neuronal responses to repellent cues. ER -