Signal Transduction Pathways
Cell signaling occurs through several different pathways, although the overall theme is that the actions of one cell influence the function of the other. Cell signaling is necessary for multicellular organisms to conduct a wide range of functions (Figlia et al., 2020). For unicellular organisms, they must identify the presence of toxic materials in their environment and respond in the most appropriate manner (Wang,2022). Identification of the different toxic materials enables them to devise survival tactics. At the same time, the presence of nutrients makes them move towards the nutrients since metabolism is necessary for reproduction and growth. Data gathered from the external environment is shared as signaling molecules commonly referred to as ligands, including ions, gases, hydrophobic molecules, and proteins.
The first step in the process is the reception which allows a cell to identify signaling molecules coming from the outside environment. According to Wachira et al. (2019), the ligands are detected when they form an attachment with the cell receptors. This can happen in two modes only, with one of them requiring the binding of receptors located in a cell with the ligands. Receptors are characterized by specific molecules that determine their response to different signals. Dopamine receptors located in the nervous system form a bond with dopamine, while insulin receptors form their bonds with insulin.
Another process is response one, where a signal triggers a specific cellular response to the message being shared by a signaling molecule. A cell can issue varying responses to a signal depending on the information being shared by a molecule. The response can happen by adding or reducing glucose intake, which either increases or decreases the metabolic process. In the resetting step, the cell goes back to its normal state after the bond between the receptor and signal molecule is broken, which stops the factors that allow a cell to respond (Procorpio et al., 2021). This happens as the cell waits for another signal to be sent, making it a necessary step that allows cells to start over and continue as they receive new signals, but only when needed to respond.
Molecular Circuits
Signal pathways follow a similar course that can be viewed in molecular circuits and can be illustrated in four steps. The first step involves the discharge of a primary messenger, which requires a signal molecule to be released. In the second step, the primary messenger is received by the cell membrane or transporters without the molecules involved entering a cell (Chapter 13, n.d). This enables the transfer of information from the outside environment to the interior parts of a cell. Regulation of signal transmission occurs by forming a complex bond between the receptor and the ligand.
The third step involves the sharing of a second messenger, which happens due to the changes that happen in the structure of receptors. This leads to the formation of small molecules that enable sharing information from the receptor-ligand complex. The small molecules are free to diffuse; hence can move to other cell compartments and influence the expression of genes (Chapter 13, n.d). The signal pathway then has a role in activating enzymes and genes that control metabolic pathways and the transmission of nerves. The molecular circuit end with the termination of the signal failure to which the ability of a cell to respond to signals can be affected significantly.
Intracellular Signaling
G proteins are a family of proteins that act as molecular switches in cells. According to Jagodzik et al. (2018), they transmit signals from various stimuli outside a cell to its interior. Since G proteins come in different types, the activities of G proteins are regulated by some factors that control their ability to bind and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP) (Pandey, 2020). A G protein attached to GTP is active, while one bound to GDP is “off” or inactive. G proteins are important in the human body since their disruption of signaling causes diseases like cholera, botulism, and pertussis (Campbell et al., 2018). The disease-causing bacteria release toxins into the cells that interrupt G protein receptor signaling.
Dimerization is a very important regulatory mechanism for receptors in a cell. Receptors initiate signal-transduction pathways through the binding of ligands. For example, the growth hormone receptor dimerizes on ligands binding, therefore, recruiting tyrosine kinases to propagate the signal. Receptor dimerization is really necessary for stimulation of the intrinsic catalytic activity. Also, some receptors undergo both homodimerization and heterodimerization, which enable the formation of proteins. There is a universal mechanism-receptor oligomerization for the activation of growth factor receptors and the activation of hormones.
The receptor tyrosine kinases (RTKs) are membrane-anchored and indirectly send signals to the nucleus. According to Butti et al. (2018), through cytoplasmic pathways, molecules finally culminate with the translocation of certain proteins from the cytoplasm activating. Receptor tyrosine kinases have a great contribution to the proliferation of cancer cells, thus promoting the epidermal growth of receptors (Poppl et al., 2021). The growth factor of the receptor is mostly found as mutated or interfered with within several types of cancer, as seen in lung, neck, and breast cancer. According to Chen et al. (2019), receptor tyrosine kinases moderate responses to a large number of signals since they include growth factors like epidermal growth factors and peptide hormones like insulin.
Calcium signaling in intracellular organisms controls many basic processes, including differentiation, proliferation, and cellular motility. The calcium levels are maintained at very low concentrations intracellularly by removing the extracellular environment in the endoplasmic reticulum (Zhang et al., 2020). Intracellular calcium concentrations increase from an inflow of extracellular calcium in the endoplasmic reticulum (Park et al. 2020). This rise induces a specific cellular response, mostly by activating some kinases to one or more proteins (Tubbs et al., 2018). Calcium is necessary for many physiological responses in the human body. They include hormone release, glycogen metabolism, neurotransmitter release, visual photo-transduction, cellular differentiation, and coagulation.
Insulin Signaling
Aging among human beings is one factor contributing to insulin signaling regulation. The aging of human beings is linked to neurophysiological changes in the brain with intellectual decrease. In diverse species, the lifespan of some pathways has been seen to be increased, while in peripheral neurons, an abnormality in insulin signaling contributes to diabetic neuropathy. Aging is associated with the binding capacity of insulin; therefore, it has a great effect on its signaling ability. Insulin signaling can also be negatively regulated by binding the adaptor protein to the kinase domain. Inadequacy in neuronal pathways is involved in developing Alzheimer’s disease (AD), a neuronal aging-related disorder associated with a decrease in insulin levels within the plasma insulin ratio (Soto et al., 2019). For neural survival, the reversing of diabetes-induced mitochondrial dysfunction is of benefit.
References
Butti, R., Das, S., Gunasekaran, V. P., Yadav, A. S., Kumar, D., & Kundu, G. C. (2018). Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications, and challenges.Molecular Cancer, 17(1), 1-18. Web.
Campbell, A. P., & Smrcka, A. V. (2018). Targeting G protein-coupled receptor signaling by blocking G proteins.Nature reviews Drug discovery, 17(11), 789-803. Web.
Chapter 13. (n.d). Signal-Transduction Pathways.
Chen, S., Xu, Z., Yang, W., Lin, X., Li, J., Li, J., & Yang, H. (2019). Logic‐Gate‐Actuated DNA‐Controlled Receptor Assembly for the Programmable Modulation of Cellular Signal Transduction. Angewandte Chemie, 131(50), 18354-18358. Web.
Figlia, G., Willnow, P., & Teleman, A. A. (2020). Metabolites regulate cell signaling and growth via covalent modification of proteins.Developmental cell, 54(2), 156-170. Web.
Jagodzik, P., Tajdel-Zielinska, M., Ciesla, A., Marczak, M., & Ludwikow, A. (2018). Mitogen-activated protein kinase cascades in plant hormone signaling. Frontiers in plant science, 9, 1387. Web.
Pandey, S. (2020). Plant receptor-like kinase signaling through heterotrimeric G-proteins. Journal of Experimental Botany, 71(5), 1742-1751. Web.
Park, Y. J., Yoo, S. A., Kim, M., & Kim, W. U. (2020). The role of calcium–calcineurin–NFAT signaling pathway in health and autoimmune diseases. Frontiers in Immunology, 11, 195. Web.
Pöppl, Á. G., Valle, S. C., Mottin, T. S., Leal, J. S., González, F. H. D., Kucharski, L. C., & Da Silva, R. S. M. (2021). Pyometra-associated insulin resistance assessment by insulin binding assay and tyrosine kinase activity evaluation in canine muscle tissue. Domestic animal endocrinology, 76, 106626. Web.
Procopio, M. C., Lauro, R., Nasso, C., Carerj, S., Squadrito, F., Bitto, A.,… & Costa, F. (2021). Role of Adenosine and Purinergic Receptors in Myocardial Infarction: Focus on Different Signal Transduction Pathways.Biomedicines, 9(2), 204. Web.
Soto, M., Cai, W., Konishi, M., & Kahn, C. R. (2019). Insulin signaling in the hippocampus and amygdala regulates metabolism and neurobehavioral. Proceedings of the National Academy of Sciences, 116(13), 6379-6384. Web.
Tubbs, E., Chanon, S., Robert, M., Bendridi, N., Bidaux, G., Chauvin, M. A.,… & Rieusset, J. (2018). Disruption of mitochondria-associated endoplasmic reticulum membrane (MAM) integrity contributes to muscle insulin resistance in mice and humans. Diabetes, 67(4), 636-650. Web.
Wachira, J., Hughes-Darden, C., & Nkwanta, A. (2019). Investigating cell signaling with gene expression datasets.Course-Source, 6. Web.
Wang, T. (2022). Exploring Single-molecule Heterogeneity and the Price of Cell Signaling (Doctoral dissertation).Case Western Reserve University. Web.
Zang, J., Zhang, T., Hussey, P. J., & Wang, P. (2020). Light microscopy of the endoplasmic reticulum–membrane contact sites in plants. Journal of Microscopy, 280(2), 134-139. Web.