Evidence for crosstalk between the extrinsic and intrinsic pathways exists in the Fas signal cascade. In most cell types, caspase-8 catalyzes the cleavage of the pro-apoptotic BH3 -only protein Bid into its truncated form, tBid. BH-3 only members of the Bcl-2 family engage exclusively anti-apoptotic members of the family (Bcl-2, Bcl-xL), allowing Bak and Bax to translocate to the outer mitochondrial membrane, thus permeabilizing it and facilitating release of pro-apoptotic proteins such as cytochrome c and Smac/DIABLO , an antagonist of inhibitors of apoptosis proteins ( IAPs ).
An overview of the Amber protein force fields, and how they were developed, can be found in: . Ponder and . Case. Force fields for protein simulations. Adv. Prot. Chem. 66, 27-85 (2003). Details on the ff14SB force field are here: . Maier, C. Martinez, K. Kasavajhala, L. Wickstrom, . Hauser and C. Simmerling. ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB. J. Chem. Theor. Comput. 11, 3696-3713 (2015). Similar information for nucleic acids is given by: . Cheatham, III and . Case. Twenty-five years of nucleic acid simulations. Biopolymers , 99, 969-977 (2013).
The effector of the G αq/11 pathway is phospholipase C-β (PLCβ), which catalyzes the cleavage of membrane-bound phosphatidylinositol 4,5-biphosphate (PIP2) into the second messengers inositol (1,4,5) trisphosphate (IP3) and diacylglycerol (DAG). IP3 acts on IP3 receptors found in the membrane of the endoplasmic reticulum (ER) to elicit Ca 2+ release from the ER, DAG diffuses along the plasma membrane where it may activate any membrane localized forms of a second ser/thr kinase called protein kinase C (PKC). Since many isoforms of PKC are also activated by increases in intracellular Ca 2+ , both these pathways can also converge on each other to signal through the same secondary effector. Elevated intracellular Ca 2+ also binds and allosterically activates proteins called calmodulins , which in turn go on to bind and allosterically activate enzymes such as Ca 2+ /calmodulin-dependent kinases (CAMKs).