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. Author manuscript; available in PMC: 2012 Mar 17.
Published in final edited form as: Behav Brain Res. 2010 Dec 13;218(1):240–247. doi: 10.1016/j.bbr.2010.12.010

Figure 1. Regulation of ERK activation in striatal neurons.

Figure 1

In striatal MSN’s, the coordinated activation of DA D1 receptors and NMDA receptors produces maximal ERK activation. D1 receptor stimulation activates cAMP-PKA, which phosphorylates the phosphoprotein DARPP-32 at its Thr-34 residue. Thr-34 DARPP-32 becomes a potent inhibitor of the phosphatase PP-1, which dephosphorylates ERK through its regulation of another phosphatase, striatal enriched phosphatase (STEP). NMDA receptor stimulation results in ca++ influx, activation of ca++ dependent kinases (not shown), which stimulates ras activity. Ras, in turn, activates raf and MEK, the kinases upstream of ERK, resulting in ERK phosphorylation. Ca++ influx also activates a signaling cascade that results in phosphorylation of DARPP-32 at Thr-75. Thr-75 DARPP-32 becomes an inhibitor of PKA activity. Green lines indicate pathways that promote ERK phosphorylation. Red lines indicate pathways that result in ERK dephosphorylation.