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Kinases: positive and negative regulators of apoptosis
1Department of Microbiology and Immunology and the Leo Jenkins Cancer Center, Brody School of Medicine at East Carolina, Greenville, NC 27858, USA.
Abstract:
Cells sense and respond to extracellular factors via receptors on the cell surface that trigger intracellular signaling pathways. The signals received by the receptors on hematopoietic cells often determine if the cell proliferates, survives or undergoes apoptosis. Apoptosis can be induced by almost any cytotoxic stimuli. These stimuli may be an absence of signals arising from cellular receptors, stimulation of specific ligand receptors on the cell surface, chemotherapeutic agents, and ionizing radiation or oxygen radicals, as well as a number of other factors. Cellular kinases and phosphatases participate in signaling cascades that influence this process. We review the ability of the calmodulin-dependent-kinases, I-kappaB kinases, PI3-kinases, Jakkinases, PKC, PKA, and MAP kinase signaling pathways (Erk, Jnk, and p38), to influence the apoptotic process. In addition, we discuss the cross-talk that exists between signaling cascades that are pro-apoptotic and anti-apoptotic.
Insights
Cellular signaling pathways regulate apoptosis, a key cell death process. This review details how various kinases, including MAP kinase pathways, influence apoptosis and interact with anti-apoptotic signals.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Cells respond to external signals through cell surface receptors that activate intracellular pathways.
- These signaling pathways are crucial for hematopoietic cell fate, determining proliferation, survival, or apoptosis.
- Apoptosis, or programmed cell death, can be triggered by diverse cytotoxic stimuli.
Purpose of the Study:
- To review the role of specific kinase signaling pathways in regulating apoptosis.
- To explore the cross-talk between pro-apoptotic and anti-apoptotic signaling cascades.
Main Methods:
- Literature review of signaling pathways involved in apoptosis.
- Analysis of the function of specific kinases and their influence on cell death.
Main Results:
- Calmodulin-dependent kinases, I-kappaB kinases, PI3-kinases, Jakkinases, PKC, PKA, and MAP kinase pathways (Erk, Jnk, p38) are key regulators of apoptosis.
- Complex cross-talk exists between signaling cascades that promote or inhibit apoptosis.
Conclusions:
- Kinase signaling pathways are central to the regulation of apoptosis in cells.
- Understanding these pathways and their interactions is vital for comprehending cell fate decisions and developing therapeutic strategies.