21.7
Amplificando Sinais via Segundos Mensageiros
Muitos ligantes de ligação ao receptor são hidrofílicos; eles não atravessam a membrana celular, mas se ligam aos receptores da superfície celular. As…
Os segundos mensageiros são moléculas não proteicas de baixo peso molecular que transmitem sinais para alvos dentro da célula quando os ligantes se ligam a receptores na superfície celular.
Os segundos mensageiros incluem íons, como íons de cálcio; nucleotídeos cíclicos, como AMP cíclico; e pequenas moléculas, como derivados de fosfato de fosfatidilinositol diacilglicerol ou DAG e trifosfato de inositol ou IP3.
Os íons de cálcio são um segundo mensageiro amplamente ocorrente. A concentração de cálcio intracelular aumenta em resposta a sinais específicos e desencadeia diversas funções fisiológicas. Por exemplo, nas células musculares, um aumento no cálcio citosólico resulta em contração muscular.
Diferentes famílias de receptores acoplados à proteína G ativam enzimas que geram segundos mensageiros, incluindo adenilil ciclase que produz AMP cíclico e fosfolipase C que produz DAG e IP3.
Esses segundos mensageiros podem ativar várias quinases a jusante, amplificando ainda mais o sinal.
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Q1: What are second messengers and why are they necessary in cell signaling?
Second messengers are low molecular weight non-protein molecules that relay signals from cell surface receptors to targets within the cell. They are necessary because many ligands are hydrophilic and cannot cross the cell membrane, so their message must be relayed by second messengers present in the cytoplasm. Examples include calcium ions, cyclic AMP, and inositol trisphosphate.
Q2: How does the phosphoinositol pathway generate second messengers?
In the phosphoinositol pathway, G protein-coupled receptors activate phospholipase C, which hydrolyzes phosphatidylinositol biphosphate (PIP2) into two second messengers: diacylglycerol (DAG) and inositol triphosphate (IP3). DAG remains near the cell membrane and activates protein kinase C, while IP3 translocates to the endoplasmic reticulum to release calcium ions.
Q3: What is the role of cyclic AMP in the cAMP signaling pathway?
Cyclic AMP (cAMP) is produced by adenylyl cyclase when activated by G protein-coupled receptors. Multiple copies of cAMP are generated from ATP molecules, allowing signal amplification. cAMP can stimulate protein kinase A, open calcium ion channels, and activate the enzyme Exchange-protein activated by cAMP (Epac).
Q4: How do second messengers amplify cellular signals?
Second messengers amplify signals by activating multiple downstream kinases and enzymes. For example, a single activated receptor can trigger adenylyl cyclase to produce many cAMP molecules, and each cAMP molecule can activate protein kinase A, creating an amplifying signals via enzymatic cascade effect that magnifies the original signal.
Q5: What is the function of calcium ions as a second messenger?
Calcium ions are widely occurring second messengers that trigger diverse physiological functions when intracellular concentration increases in response to specific signals. In muscle cells, increased cytosolic calcium results in muscle contraction. Calcium can be released from the endoplasmic reticulum through IP3-activated channels or through other calcium ion channels.
Q6: How does PIP3 differ from other second messengers in growth factor signaling?
Phosphatidylinositol triphosphate (PIP3) is a second messenger derived from phosphorylation of PIP2 when growth factors bind receptor tyrosine kinases. Unlike other second messengers, PIP3 recruits Akt (protein kinase B) to the membrane, where it regulates cell survival pathways including proliferation, apoptosis, and migration.
Q7: What is cyclic GMP and how does it compare to cyclic AMP?
Cyclic GMP (cGMP) is synthesized from GTP when guanylyl cyclase is activated, similar to how cAMP is produced. As a second messenger, cGMP induces protein kinase G (PKG), which has overlapping functions with protein kinase A. However, PKG expression is restricted to vascular tissues, lungs, and the brain, limiting cGMP's physiological scope.