External Ligands

External ligands are molecules located outside a cell that bind specifically to cell surface receptors, initiating a cellular response. They are often signaling molecules that help regulate a wide range of biological processes, such as growth, immune response, metabolism, differentiation, and communication between cells.

Key Characteristics:

• Extracellular: Present outside the cell membrane.
• Specificity: Bind selectively to specific cell surface receptors (e.g., integrins, GPCRs, RTKs).
• Trigger signaling cascades: Ligand binding usually initiates an intracellular signaling pathway.
• Can be soluble, membrane-bound, or part of the extracellular matrix (ECM).

Types of External Ligands:

Mechanism of Action:

1. Ligand binds to a receptor on the cell surface (e.g., a G protein-coupled receptor or integrin).
2. This causes a conformational change in the receptor.
3. The change initiates an intracellular signaling cascade (e.g., activation of kinases, second messengers like cAMP or calcium).
4. The signal leads to a cellular response such as gene expression, secretion, migration, or apoptosis.

Examples of Ligand-Receptor Pairs:

Clinical Relevance:

• Cancer: Overexpression or mutation of ligand or receptor genes can drive uncontrolled growth (e.g., EGF/EGFR).
• Autoimmune disease: Misrecognition of external ligands (e.g., self-antigens) can trigger immune attacks.
• Drug targets: Many drugs act as ligands that mimic or block natural ligands (e.g., beta-blockers, monoclonal antibodies).
• Vaccine development: Uses external ligands (antigens) to trigger immune responses safely.

Summary Table: