Cells communicate by releasing extracellular signaling molecules (e.g., hormones and neurotransmitters) that bind to receptor proteins located in the plasma membrane, cytoplasm, or nucleus. This signal is transduced into the activation, or inactivation, of one or more intracellular messengers by interacting with receptors. Receptors interact with a variety of intracellular signaling proteins, including kinases, phosphatases, and guanosine triphosphate (GTP)–binding proteins (G proteins). These signaling proteins interact with and regulate the activity of target proteins and thereby modulate cellular function.

Signaling pathways are characterized by multiple, hierarchical steps, amplification of the signal-receptor binding event, which magnifies the response, and activation of multiple pathways and regulation of multiple cellular functions. Mechanisms are in place to minimize the response and provide tight regulatory control over these signaling pathways. 

Cells in higher animals release hundreds of chemicals into the extracellular space. These include peptides and proteins (e.g., insulin), amines (e.g., epinephrine and norepinephrine), steroid hormones (e.g., aldosterone, estrogen), and small molecules such as amino acids, nucleotides, ions (e.g., Ca++), and gases like nitric oxide and carbon dioxide. The secretion of these signaling molecules occurs through different mechanisms.

A signaling molecule, which can be a hormone or neurotransmitter, binds to a receptor located in the plasma membrane, cytosol, or nucleus. This binding activates intracellular signaling proteins that interact with and regulate the activity of target proteins, leading to changes in cellular function. Signaling molecules play a role in regulating cell growth, division, and differentiation, as well as influencing cellular metabolism. They also modulate the intracellular ionic composition by regulating the activity of ion channels and transport proteins. Furthermore, signaling molecules control various cytoskeleton-associated events, including cell shape, division, migration, and adhesion between cells and the extracellular matrix.

The ability of a cell to respond to a specific signaling molecule depends on the expression of receptors with high affinity and specificity for that molecule. Receptors can be found in the plasma membrane, cytosol, and nucleus. Contact-dependent signaling occurs when a membrane-bound signaling molecule from one cell binds directly to a plasma membrane receptor on another cell. This type of signaling is important during development, immune responses, and in cancer. Molecules that are released and act locally are referred to as paracrine signaling.
Fig. 3.1 . Cells communicate by releasing extracellular signaling molecules (e.g., hormones and neurotransmitters) that bind to receptor proteins located in the plasma membrane, cytoplasm, or nucleus. This signal is transduced into the activation, or inactivation, of one or more intracellular messengers by interacting with receptors. Receptors interact with a variety of intracellular signaling proteins, including kinases, phosphatases, and guanosine triphosphate (GTP)–binding proteins (G proteins). These signaling proteins interact with and regulate the activity of target proteins and thereby modulate cellular function. Target proteins include, but are not limited to, ion channels and other transport proteins, metabolic enzymes, cytoskeletal proteins, gene regulatory proteins, and cell cycle proteins that regulate cell growth and division. Signaling pathways are characterized by (1) multiple, hierarchical steps; (2) amplification of the signal-receptor binding event, which magnifies the response; (3) activation of multiple pathways and regulation of multiple cellular functions; mechanisms, which minimize the response and provide tight regulatory control over these signaling pathways. A brief description of how cells communicate follows. Readers who desire a more in-depth presentation of this material are encouraged to consult one of the many cellular and molecular biology textbooks currently available.
Cells in higher animals release into the extracellular space hundreds of chemicals, including (1) peptides and proteins (e.g., insulin); (2) amines (e.g., epinephrine and norepinephrine); (3) steroid hormones (e.g., aldosterone, estrogen); and (4) small molecules, including amino acids, nucleotides, ions (e.g., Ca++), and gases, such as nitric oxide and carbon dioxide. Secretion of signaling molecules is • Fig. 3.1 An Overview of How Cells Communicate. A signaling molecule (i.e., hormone or neurotransmitter) binds to a receptor, which may be in the plasma membrane, cytosol, or nucleus. Binding of ligand to a receptor activates intracellular signaling proteins, which interact with and regulate the activity of one or more target proteins to change cellular function. Signaling molecules regulate cell growth, division, and differentiation and influence cellular metabolism. In addition, they modulate the intracellular ionic composition by regulating the activity of ion channels and transport proteins. Signaling molecules also control cytoskeleton-associated events, including cell shape, division, and migration and cell-to-cell and cell-to-matrix adhesion. (Redrawn from Alberts B, et al: Molecular Biology of the Cell. 6th ed. New York: Garland Science; 2015.)
CHAPTER 3 Signal Transduction, Membrane Receptors, Second Messengers, and Regulation of Gene Expression 37 cell-type specific. For example, beta cells in the pancreas release insulin, which stimulates glucose uptake into cells. The ability of a cell to respond to a specific signaling molecule depends on the expression of receptors that bind the signaling molecule with high affinity and specificity. Receptors are located in the plasma membrane, the cytosol, and the nucleus (
Fig. 3.2
Fig. 3.3).
Contact-dependent signaling, in which a membrane-bound signaling molecule of one cell binds directly to a plasma membrane receptor of another cell, is important during development, in immune responses, and in cancer (see
Fig. 3.3A ). Molecules that are released and act locally are called paracrine (see
Fig. 3.3B