Fig. (2) Regulation of mRNA stability by p38 MAPK and TTP. Most mRNAs are modified by the addition of a 7-methyl guanisine (m7G cap) at the 5' end, and a poly adenosine or poly(A) tail at the 3' end. The protein coding open reading frame (ORF) is flanked by 5' and 3' untranslated regions (UTRs). Adenosine/uridine rich elements (AREs) in the 3' UTRs of many cytokine mRNAs are specifically recognized by tristetraprolin (TTP), which then recruits the CCR4/NOT deadenylase complex. This complex catalyzes the removal of the poly(A) tail and initiates the degradation of the mRNA body. Following its activation by p38 MAPK, MAPK-activated protein kinase 2 (MK2) phosphorylates serines 52 and 178 of TTP, preventing the recruitment of the deadenylase complex and thus stabilizing mRNAs that are recognized by TTP.