Table 1.

SOCS2:TrkA interaction and outcome summary.

	Outcome of increased SOCS2 expression
	No NGF	With NGF
Survival	No change (DRG)	No change (DRG)
Neurite outgrowth	Increased ↑ (PC12)	Increased ↑↑ (PC12 and DRG)
TrkA: total protein levels	Increased ↑ (PC12 and 293T)	Increased ↑ (PC12 and 293T)
TrkA: surface protein levels	Increased ↑ (PC12 and DRG)	Increased ↑ (PC12) No change (DRG)
Signaling: pTrkA, pAKT, pERK1/2	pERK1/2 Increased ↑ Others no change (PC12)	Increased ↑ (PC12)

Increased expression of SOCS2 (relative to endogenous levels of SOCS2), either in SOCS2TG mice (DRG neurons) or by transfection of cell lines (PC12 and 293T cells) alters the outcome of NGF-induced signaling. Increased SOCS2 does not affect NGF-mediated DRG neuron survival, with equivalent levels of survival with NGF and cell death in the absence of NGF. However, increased SOCS2 levels promote increased neurite outgrowth under basal conditions, which is further enhanced by NGF. It also increases total and surface TrkA levels (in PC12 cells the increased surface levels correlate with increased total levels) and increases the level and duration of signaling via the PI-3 kinase (AKT) and ERK1/2 pathways. The mechanism for this differential outcome of SOCS2 on NGF-mediated survival vs. neurite outgrowth remains to be determined, as does how SOCS2 influences neurite outgrowth, but likely involves ubiquitination and altered TrkA cellular localization due to the E3 ubiquitin ligase activity of the SOCS box.