Signal transduction pathways model

A study of the molecular descriptions provided by geneticists and molecular biologists reveals at least three different levels. The first can be illustrated by the schematic models of signal-transduction pathways. In such models, the precise shape of the different proteins, their atomic composition, is of no importance. Sometimes, only the name of the protein is given. What is important is the place of these proteins in the pathways, how they receive upstream signals and transfer them to downstream molecular components. 

A property of the protein kinase C enzyme family that is highly valuable for their identification and characterization is their activation by tumor promoters such as phorbol esters (Fig. 7.7). Protein kinase C binds to the tumor promoter, tetradecanoyl phorbol acetate (TPA), with high affinity and is activated by this binding. The specific activation of protein kinase C by phorbol esters is an important tool to demonstrate their involvement in signal transduction pathways. By external addition of TPA, it is possible to use cellular model systems to test which biological responses of a signal transduction pathway involve, and are controlled by, protein kinase C. 

Impairment of the retinoid signal transduction pathways occurs as a result of prolonged UV exposure. Down regulation of nuclear receptors for Vitamin A occurs,269 resulting in a functional deficiency of Vitamin A. Application of Vitamin A derivatives would appear to be an obvious treatment modality. Topical application of Vitamin A does increase the HA in the epidermal layer, increasing the thickness of the HA meshwork after prolonged treatment.270 Vitamin A thus enhances repair, as can be demonstrated in photo-aged hairless mouse model.271 The decline in GAG, and in particular HA deposition that occurs with UVB irradiation, can be entirely prevented by retinoic acid treatment. 

Suresh Babu CV, Joo Song E, Yoo YS (2006) Modeling and simulation in signal transduction pathways a systems biology approach. Biochimie 88 277-283... 

Fig. 5. Model for elicitor signal transduction leading to Str expression. The model shows the positions of CrBPF-1 in a JA-independent, and ORCAs in a JA-dependent, elicitor signal transduction pathway. Protein phosphorylation and calcium influx are required for elicitor-induced jasmonate biosynthesis, as well as for the induction of CrBPF-1, ORCA2, and ORCA3. ORCA activation additionally depends on jasmonate biosynthesis. The positions of the TATA box, the BA region, and the jasmonate- and elicitor-responsive element (JERE) within the Str promoter are indicated...

Acute high-altitude studies of both human and animal models indicate that hypoxia defenses are initiated by several oxygen sensing, signal transduction pathways. For convenience, these have been summarized as five general hypoxia response systems (figure 5.2(A)-(E) ... 

It has been shown in cell culture models of cXj-antitrypsin that Z-oq-antitrypsin in the ER causes expression of a novel set of stress genes with products that have the role of restoring ER function to normal. Z-a,-Antitrypsin induces two signal transduction pathways the ER overload response and unfolded protein response pathways. Via these transduction pathways, the presence of Z-oq-antitrypsin, as opposed to M-(Xj-antitrypsin, induces an hepatic inflammatory response. It is thought that this ER-specific stress response results in hepatic injury. 

Mathematical models are widely applied in biosciences and different modeling routes can be taken to describe biological systems. The type of model to use depends completely on the objective of the study. Models can be dynamic or static, deterministic or stochastic. Kinetic models are commonly used to study transient states of the cell such as the cell cycle [101] or signal transduction pathways [102], whereas stoichiometric models are generally used when kinetics parameters are unknown and steady state systems is assumed [48, 103]. 

---