Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The AMP-activated protein kinase (AMPK) is a metabolite sensing serine/threonine kinase that has been termed the master regulator of cellular energy metabolism due to its numerous roles in the regulation of glucose, lipid, and protein metabolism. In this review, we first summarize the current literature on a number of important aspects of AMPK in skeletal muscle. These include the following: (1) the structural components of the three AMPK subunits (i.e. AMPKalpha, beta, and gamma), and their differential localization in response to stimulation in muscle; (2) the biochemical regulation of AMPK by AMP, protein phosphatases, and its three known upstream kinases, LKB1, Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), and transforming growth factor-beta-activated kinase 1 (TAK1); (3) the pharmacological agents that are currently available for the activation and inhibition of AMPK; (4) the physiological stimuli that activate AMPK in muscle; and (5) the metabolic processes that AMPK regulates in skeletal muscle.
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PMID:AMP-activated protein kinase in skeletal muscle: from structure and localization to its role as a master regulator of cellular metabolism. 1881 Mar 25

Promoting apoptosis is a strategy for cancer drug discovery. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a wide range of malignant cells. However, several cancers, including human hepatocellular carcinoma (HCC), exhibit a major resistance to TRAIL-induced cell death. Melittin, a water-soluble 26-amino acid peptide derived from bee venom of Apis mellifera, can exert toxic or inhibitory effects on many types of tumor cells. Here we report that melittin can induce apoptosis of HCC cells by activating Ca2+/calmodulin-dependent protein kinase, transforming growth factor-beta-activated kinase 1 (TAK1), and JNK/p38 MAPK. We show that melittin-induced apoptosis can be inhibited by calcium chelator, by inhibitors for Ca2+/calmodulin-dependent protein kinase, JNK and p38, and by dominant negative TAK1. In the presence of melittin, TRAIL-induced apoptosis is significantly increased in TRAIL-resistant HCC cells, which may be attributed to melittin-induced TAK1-JNK/p38 activation and melittin-mediated inhibition of IkappaBalpha kinase-NFkappaB. Our data suggest that melittin can synergize with TRAIL in the induction of HCC cell apoptosis by activating the TAK1-JNK/p38 pathway but inhibiting the IkappaBalpha kinase-NFkappaB pathway. Therefore, the combination of melittin with TRAIL may be a promising therapeutic approach in the treatment of TRAIL-resistant human cancer.
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PMID:Melittin, a major component of bee venom, sensitizes human hepatocellular carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by activating CaMKII-TAK1-JNK/p38 and inhibiting IkappaBalpha kinase-NFkappaB. 3259 56