factors are downstream targets of p38α MAPK, including ATF1/2/6, c-Myc, c-FOS, GATA4, MEF2A/C, SRF, STAT1, and CHOP Role in cardiovascular system p38α MAPK constitutes the main p38 MAPK activity in heart. During cardiomyocyte maturation in new born mouse heart, p38α MAPK activity can regulate myocyte cytokinesis and promote cell cycle exit. while inhibition of p38 MAPK activity leads to induction of mitosis in both adult and fetal cardiomyocyte. Therefore, p38 MAPK is associated with cell-cycle arrest in mammalian cardiomyocytes and its inhibition may represent a strategy to promote cardiac regeneration in response to injury. In addition, p38α MAPK induction promotes myocyte apoptosis. via downstream targets STAT1, CHOP, FAK, SMAD, cytochrome c, NF-κB, PTEN, and p53. p38 MAPK can also target IRS-1 mediated AKT signaling and promotes myocyte death under chronic insulin stimulation. Inhibition of p38 MAPK activity confers cardioprotection against ischemia reperfusion injury in heart However, some reports demonstrated that p38 MAPK also involves in anti-apoptotic effect via phosphorylation of αβ-Crystallin or induction of Pim-3 during early response to oxidative stress or anoxic preconditioning respectively Both p38α MAPK and p38β MAPK appear to have an opposite role in apoptosis. Whereas p38α MAPK has a pro-apoptotic role via p53 activation, p38β MAPK has a pro-survival role via inhibition of ROS formation. In general, chronic activation of p38 MAPK activity is viewed as pathological and pro-apoptotic, and inhibition of p38 MAPK activity is in clinical evaluation as a potential therapy to mitigate acute injury in ischemic heart failure. p38 MAPK activity is also implicated in cardiac hypertrophy which is a significant feature of pathological remodeling in the diseased hearts and a major risk factor for heart failure and advert outcome. Most in vitro evidence supports that p38 MAPK activation promotes cardiomyocyte hypertrophy. However, in vivo evidence suggest that chronic activation of p38 MAPK activity triggers restrictive cardiomyopathy with limited hypertrophy, while genetic inactivation p38α MAPK in mouse heart results in an elevated cardiac hypertrophy in response to pressure overload or swimming exercise. Therefore, the functional role of p38 MAPK in cardiac hypertrophy remains controversial and yet to be further elucidated. Interactions MAPK14 has been shown to interact with: AKT1, ATF2, CDC25B, CDC25C, CSNK2A1, DUSP10, DUSP16, DUSP1, FUBP1, HTRA2, KRT8 MAP2K6, TAB1, MAPK1, MAPKAPK2, MAPKAPK3, MEF2A, RPS6KA4, and ZFP36L1. Notes References Further reading External links MAP Kinase Resource . EC 2.7.11