Cellular Signaling Pathways

Cellular signaling pathways are essential for how cells communicate and respond to their environment. These pathways, like GPCRs and RTKs, involve complex interactions that regulate vital processes, linking biophysics to cellular function and health. Understanding these mechanisms is crucial for grasping biological systems.

1. G protein-coupled receptor (GPCR) signaling

   • GPCRs are a large family of membrane receptors that detect molecules outside the cell and activate internal signal transduction pathways.
   • They work through the activation of G proteins, which are molecular switches that relay signals from the receptor to various intracellular effectors.
   • GPCR signaling is involved in numerous physiological processes, including sensory perception, immune responses, and mood regulation.

2. Receptor tyrosine kinase (RTK) signaling

   • RTKs are a class of cell surface receptors that, upon binding to their ligands, undergo dimerization and autophosphorylation, activating downstream signaling cascades.
   • They play a crucial role in regulating cell growth, differentiation, and metabolism.
   • Dysregulation of RTK signaling is often implicated in cancer and other diseases.

3. Ion channel-linked receptor signaling

   • These receptors are directly linked to ion channels, allowing ions to flow across the membrane in response to ligand binding.
   • They are essential for rapid signaling in neurons and muscle cells, contributing to processes like synaptic transmission and muscle contraction.
   • The opening or closing of these channels alters the membrane potential, leading to cellular responses.

4. JAK-STAT signaling pathway

   • This pathway involves Janus kinases (JAKs) that phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) in response to cytokine signaling.
   • Activated STATs translocate to the nucleus to regulate gene expression, influencing immune responses and cell growth.
   • JAK-STAT signaling is critical for hematopoiesis and the immune system.

5. MAPK/ERK pathway

   • The MAPK/ERK pathway transmits signals from the cell surface to the nucleus, regulating cell division, differentiation, and survival.
   • It is activated by various growth factors and cytokines, leading to a cascade of phosphorylation events involving MAP kinases.
   • Aberrant activation of this pathway is associated with cancer progression.

6. PI3K-Akt pathway

   • This signaling pathway is activated by growth factors and plays a key role in cell survival, growth, and metabolism.
   • Phosphoinositide 3-kinase (PI3K) generates lipid second messengers that activate Akt, a serine/threonine kinase.
   • The PI3K-Akt pathway is often dysregulated in cancer, promoting cell proliferation and survival.

7. cAMP signaling pathway

   • Cyclic adenosine monophosphate (cAMP) acts as a second messenger in various signaling pathways, mediating the effects of hormones like adrenaline.
   • It activates protein kinase A (PKA), which phosphorylates target proteins to elicit cellular responses.
   • cAMP signaling is involved in regulating metabolism, gene expression, and neuronal signaling.

8. Calcium signaling

   • Calcium ions serve as vital secondary messengers in many signaling pathways, influencing processes such as muscle contraction, neurotransmitter release, and cell division.
   • Calcium levels are tightly regulated by channels, pumps, and storage in the endoplasmic reticulum.
   • Changes in intracellular calcium concentrations can trigger various cellular responses, including activation of calcium-dependent proteins.

9. Wnt signaling pathway

   • Wnt signaling is crucial for embryonic development, cell differentiation, and tissue homeostasis.
   • It involves the binding of Wnt proteins to Frizzled receptors, leading to stabilization of β-catenin and activation of target gene transcription.
   • Dysregulation of Wnt signaling is linked to developmental disorders and cancer.

10. NF-κB signaling pathway

    • NF-κB is a transcription factor that regulates immune response, inflammation, and cell survival.
    • It is activated by various stimuli, including cytokines and stress signals, leading to the phosphorylation and degradation of IκB proteins.
    • Once released, NF-κB translocates to the nucleus to initiate the transcription of target genes involved in immune and inflammatory responses.