Notes

In paracrine signaling, the signaling molecules released by a cell affect

only those target cells in close proximity.

An example is a neuron releasing a neurotransmitter that acts on an adjacent

neuron. In addition to neurotransmitters, many of the protein growth factors

that regulate development in multicellular organisms act at short range.

Several of the developmentally important signaling proteins diffuse away

from the signaling cell, forming a concentration gradient, and induce

different responses in nearby cells depending on their distances from

the signaling cells and thus on the local concentration of the signaling

protein.

In some cases, paracrine signaling molecules, exemplified by TGF-

β, are secreted by a cell and then trapped nearby in the web of extracellular

macromolecules termed the extracellular matrix until freed to bind to

cellsurface receptors on a nearby cell.

In autocrine signaling, cells respond to substances that they themselves

release. This type of signaling is particularly characteristic of tumor cells.

Many tumor cells release growth factors that stimulate inappropriate,

unregulated self-proliferation.

Some signaling molecules are integral membrane proteins located on the

cell surface. The targets of these relatively immobile membrane signals are

receptors on the surface of adjacent cells, whose proliferation or

differentiation are controlled by the signal.

In other cases, proteolytic cleavage of a membrane-bound signaling protein

releases the extracellular domain, which functions as a soluble signaling

molecule that can act locally or at a distance.

Some signaling molecules can act at both short and long ranges. For

example, epinephrine (also known as adrenaline) functions as a

neurotransmitter (paracrine signaling) and as a hormone (endocrine

signaling). As a hormone, it helps initiate the fight-or-flight response to a

sudden danger in the environment.

The effector proteins in signal transduction pathways are often enzymes or

transcription factors that induce two major types of cellular responses: rapid
short-term changes in protein activities (seconds-to-minutes) or slower

long-term changes (hours-to-days).

Rapid changes are typically

consequences of modifications to specific preexisting enzymes and other

proteins that alter their activity or function.

Changes to these proteins are often initiated by covalent modifications such

as phosphorylation or ubiquitinylation or by binding of ions or molecules

such as or cAMP. Such modifications can induce changes in cellular

metabolism of sugars, amino acids, and lipids; can induce secretion of

hormones; and can induce in nerve cells the electric signals called action

potentials

Slower, long-term changes are typically consequences of changes in gene

expression, either activating or inhibiting synthesis of specific proteins.