Signal Transduction - Major Pathways

Major Pathways

Following are some major signaling pathways, demonstrating how ligands binding to their receptors can affect second messengers and eventually result in altered cellular responses.

• MAPK/ERK pathway: A pathway that couples intracellular responses to the binding of growth factors to cell surface receptors. This pathway is very complex and includes many protein components. In many cell types, activation of this pathway promotes cell division, and many forms of cancer are associated with aberrations in it.

• cAMP dependent pathway: In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein kinase) (see picture), and thus, further effects mainly depend on cAMP-dependent protein kinase, which vary based on the type of cell.

• IP₃/DAG pathway: PLC cleaves the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) yielding diacyl glycerol (DAG) and inositol 1,4,5-triphosphate (IP₃). DAG remains bound to the membrane, and IP₃ is released as a soluble structure into the cytosol. IP₃ then diffuses through the cytosol to bind to IP₃ receptors, particular calcium channels in the endoplasmic reticulum (ER). These channels are specific to calcium and only allow the passage of calcium to move through. This causes the cytosolic concentration of Calcium to increase, causing a cascade of intracellular changes and activity. In addition, calcium and DAG together works to activate PKC, which goes on to phosphorylate other molecules, leading to altered cellular activity. End effects include taste, manic depression, tumor promotion, etc.