Thyroid hormone (T(3)) regulates the function of many tissues within the body. 
The effects of T(3) have largely been attributed to the modulation of thyroid 
hormone receptor-dependent gene transcription. However, nongenomic actions of 
T(3) via the initiation of signaling events are emerging in a number of cell 
types. This study investigated the ability of short-term T(3) treatment to 
phosphorylate and, therefore, activate signaling proteins in rat tissues in 
vivo. The kinases investigated included p38, AMP-activated protein kinase 
(AMPK), and extracellular signal-regulated kinase (ERK) 1/2. Following 2 h of 
T(3) treatment, p38 and AMPK phosphorylation was increased in both the 
slow-twitch soleus and the fast-twitch plantaris muscles. In contrast, ERK1/2 
was not activated in either muscle type. Neither p38 nor AMPK was affected in 
heart. However, AMPK activation was decreased by T(3) in liver. ERK1/2 
activation was decreased by T(3) in heart, but increased in liver. Possible 
downstream consequences of T(3)-induced kinase phosphorylation were investigated 
by measuring cAMP response element binding protein (CREB) and thyroid hormone 
receptor DNA binding, as well as peroxisome proliferator-activated 
receptor-alpha coactivator-1 mRNA levels. Protein DNA binding to the cAMP or 
thyroid hormone response elements was unaltered by T(3). However, peroxisome 
proliferator-activated receptor-alpha coactivator-1 mRNA expression was 
increased following 12 h of T(3) treatment in soleus. These data are the first 
to characterize the effects of T(3) treatment on kinase phosphorylation in vivo. 
We show that T(3) rapidly modifies kinase activity in a tissue-specific fashion. 
Moreover, the T(3)-induced phosphorylation of p38 and AMPK in both slow- and 
fast-twitch skeletal muscles suggests that these events may be important in 
mediating hormone-induced increases in mitochondrial biogenesis in skeletal 
muscle.