Biol 3090 Lecture 12 (Signal Transduction)

Second messengers

Intracellular signaling molecules which relay the signal to the inside of the cell

Effector proteins

Lie at the end of signaling pathways; bring about a change in cellular function/behavior

Signal transduction

An extracellular signal (first messenger) is detected by a receptor on a target cell, second messengers relay the signal to the inside, and effector proteins then bring about a change in cellular function/behavior.

Contact-dependent signaling

Signals remain bound to a "sending cell," and thus influence only target cells that the sending cell directly interacts with.

Paracrine signaling

Signals are secreted to the extracellular fluid by the sending cell, but act as local mediators to influence only nearby target cells

Endocrine signaling

Signals are secreted to the extracellular fluid by the sending cell, and travel long distances (such as through the bloodstream) to target cells that are far away (example: hormones)

Molecular switch

Upon receipt of a signal, proteins can switch from an inactive to an active state, until another process turns them off.

Phosphorylation

The transfer of a phosphate group, usually from ATP, to a molecule. Often, this is activating, but it may also be deactivating.

Kinase

Enzyme that transfers phosphate groups

Phosphatase

Enzyme that removes a phosphate group

GEF

Guanine nucleotide exchange factor. Dislodges GDP and allows GTP to bind in its place.

GAP

GTPase activating protein

Double-negative activation

Inhibition of an inhibitor activates a downstream protein.

Scaffold proteins

Bring together signaling molecules into complexes; enhance efficiency by localizing signaling molecules in the same cell, thus ensuring that proteins interact with each other and not with inappropriate partners

Interaction domains

Recognize a structural motif in another molecule (such as another domain, or a covalent modification); these are modular, and thus can connect multiple pathways

All-or-none response

A switchlike response, in which the cell abruptly changes between a high and low response (with no intermediate) once the signal reaches a threshold concentration

Hyperbolic response

A response that increases gradually with increasing signal concentrations, until saturation of the system (the response reaches a plateau at this point)

Sigmoidal response

A response that is reduced (but not absent) at low signal concentrations, but then increases steeply at an intermediate signal concentration; provides a "filter" against low-level background signal

Positive feedback

The output stimulates its own production

Negative feedback

The output inhibits its own production

Desensitization

AKA adaptation, prolonged exposure to a stimulus decreases a cell's response to that level of stimulus

G-protein

Composed of an alpha, beta, and gamma subunit. When unstimulated, all three are in a complex, and the alpha subunit is bound by GDP. May be activated by a GPCR or GEF disodging GDP and allowing GTP to bind in its place.

G-protein coupled receptors

When activated, acts like a GEF (guanine nucleotide exchange factor) to dislodge GDP and allow GTP to bind in its place. This does two things:
1.) releases the G protein from its coupled receptor
2.) dissociates the alpha subunit from the beta and gamma subunits (which stay together)
Both the isolated alpha subunit and the beta-gamma pair can then interact with targets (such as channels and enzymes) to relay the signal onward to effectors.

Enzyme-coupled receptors

Either act as enzymes or are directly linked to enzymes. Typically only have one transmembrane segment, but can associate as dimers.

Adenylyl cyclase

Synthesizes cyclic AMP from ATP

Cyclic AMP

A second messenger derived from ATP and triggers specific cellular changes in metabolic regulation

Cyclic-AMP-dependent protein kinase

PKA. Active PKA can phosphorylate and activate various effector proteins (such as transcription factors, which then modulate gene expression)

Receptor tyrosine kinases

RTKs. Enzyme coupled receptors that:
1.) Usually exist as monomers
2.) Upon signal binding, they form a dimer and phosphorylate each other (on tyrosine residues)
3.) This leads to more phosphorylation, and recruitment of signaling proteins by phosphotyrosine-binding domains (SH2 domains, for example)

MAP kinase kinase

Kinase that phosphorylates MAP kinase

MAP kinase kinase kinase

Kinase that phosphorylates MAP kinase kinase