Hormones and Cell Signaling

Hormones and Cell Signaling

• The term "hormone" comes from the Greek word "hermon", meaning "to excite or set into motion".
• Hormones are chemicals produced in one area of the body that have an effect on another area.
• Hormones are named based on their effect on the body, not their location of production.

Types of Hormone Signaling

• Autocrine signaling: ligands function internally and on other target cells.
• Paracrine signaling: ligands target cells only in the vicinity of the original emitting cell.
• Endocrine signaling: hormones that target distant cells and often travel through the circulatory system.
• Intracrine signaling: ligands are produced by the target cell and bind to a receptor within the cell.
• Juxtacrine signaling: ligands target adjacent cells.

Cell Signaling Mechanisms

• Each cell type displays a set of receptors that enable it to respond to a set of signal molecules.
• An individual cell often requires multiple signals to survive, grow, and differentiate.
• If deprived of appropriate survival signals, a cell will undergo apoptosis (cell suicide).

Receptor Signaling

• A receptor and some intracellular signaling proteins are preassembled into a signaling complex on the inactive receptor.
• The activated receptor phosphorylates itself at multiple sites, which then act as docking sites for intracellular signaling proteins.
• Activation of a receptor leads to the increased phosphorylation of specific phospholipids in the adjacent plasma membrane.

Intracellular Signaling Proteins

• Types of interaction domains in signaling proteins:
  • Src homology 2 (SH2) domains
  • Phosphotyrosine-binding (PTB) domains
  • Src homology 3 (SH3) domains
  • Pleckstrin homology (PH) domains

Signaling Systems

• Response timing varies in different signaling systems, according to the speed required for the response.
• Sensitivity to extracellular signals varies greatly, with hormones acting at very low concentrations on distant target cells.
• Signal amplification is a mechanism for increasing the sensitivity of a signaling system.
• Dynamic range of a signaling system is related to its sensitivity, with some systems responding over a narrow range of extracellular signal concentrations and others over a broader range.

Signal Processing

• Signal processing can convert a simple signal into a complex response, such as an abrupt, switch-like response or an oscillatory response.
• Feedback lies at the heart of biochemical switches and oscillators.
• Integration allows a response to be governed by multiple inputs.

Coordination of Multiple Responses

• Coordination of multiple responses in one cell can be achieved by a single extracellular signal.
• Coordination depends on mechanisms for distributing a signal to multiple effectors, including branches in the signaling pathway.

Hormone Synthesis and Processing

• Many protein and peptide hormones are synthesized within a larger precursor protein.
• The process is catalyzed by specific proteases that cleave the protein at specific sites.
• Alternative splicing of mRNA for hormones can also occur.

Receptor Structure

• A receptor typically consists of a ligand-binding domain that noncovalently binds the correct hormone and an effector domain that responds to the presence of the hormone bound to the ligand domain.

Zinc Finger Proteins

• The coordination of a Zn2+ atom by four cysteines causes the formation of a loop in zinc finger proteins.
• The P-box in the first zinc finger is involved in binding to specific DNA binding sites and discriminating between closely related sites for different hormones.

G Proteins and Ion Channels

• Smell and vision depend on GPCRs that regulate ion channels.
• Olfactory receptor neurons possess modified cilia that contain the olfactory receptors and the signal transduction machinery.
• The axon of the receptor neuron conveys electrical signals to the brain when an odorant activates the cell to produce an action potential.