This refers to the complex, multi-step sequence of molecular events initiated by an extracellular signal, such as a hormone or growth factor, that ultimately results in a coordinated, body-wide (systemic) physiological response. These cascades involve a relay of signals through a series of kinases, second messengers, and transcription factors, ensuring signal amplification and integration across different tissues and organs. Understanding these cascades is essential for clinical practice as they govern processes like metabolism, growth, stress response, and immune function. Disruption of these signaling networks is often the root cause of metabolic and endocrine disorders.
Origin
The term is fundamental to cell biology and endocrinology, combining ‘systemic,’ referring to the whole organism, with ‘signaling cascades,’ describing the sequential nature of signal transduction. The concept of hormones acting as messengers to initiate a cascade dates back to early endocrinology, but the molecular detail of the intracellular steps has been elucidated over the past decades. This framework is used to describe the hierarchical communication between the neuroendocrine axis and peripheral target cells.
Mechanism
A cascade begins with a first messenger binding to a cell-surface receptor, which activates a G-protein or a receptor tyrosine kinase. This activation generates a second messenger, such as cAMP or DAG, which then activates a protein kinase, like PKA or PKC. The kinase then phosphorylates numerous downstream effector proteins, including enzymes and transcription factors, leading to a massive amplification of the initial signal. This final step results in altered gene expression and protein activity, producing the coordinated systemic physiological change, such as glucose mobilization or tissue repair.
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