The guanine nucleotide exchange factor EPAC1 is another effector of cAMP in T cells (215, 216). cAMP binds to the cAMP-responsive N-terminal region of EPAC1 and induces an open conformation rendering its catalytic core accessible to its effectors (217, 218). The most heavily characterized EPAC1 effector in T cells is the anergy-associated GTPase Rap1 (219, 220) which in its GTP-bound form is targeted to the plasma membrane (221) where it inhibits TCR-induced MEK-ERK activation by sequestering Raf-1 (220, 222).