Signal Transduction and Cell Signaling Concepts

autocrine signaling

A cell releases signals that bind to its own receptors.

paracrine signaling

Signal diffuses locally to nearby cells.

endocrine signaling

Hormones travel through the bloodstream to distant targets.

ligand binding to a receptor

It triggers a relay cascade involving second messengers, enzymes, and kinases, ending with a target protein response.

second messenger pathway

Ligand binds receptor, activates enzyme, produces second messenger (e.g., cAMP) which activates proteins.

protein recruitment pathway

Ligand binds receptor, which recruits proteins to the membrane for direct action.

kinase cascade pathway

Phosphorylation events cascade through kinases to activate downstream proteins.

function of kinases

Kinases add phosphate groups to proteins, affecting activity, localization, stability, and interactions.

function of phosphatases

Phosphatases remove phosphate groups from proteins.

phosphorylated residues

Serine, Threonine, and Tyrosine.

GPCR functions

Vision, smell, taste, mood regulation.

RTKs

Cell growth and differentiation via kinase activity.

ion channels

Ligand-gated synaptic signaling.

role of integrins

Cell adhesion and mechanical signaling.

intracellular receptors

Steroid hormones and nitric oxide, affecting gene expression.

structure of GPCRs

7-transmembrane alpha-helices that interact with G-proteins.

GPCR activation of G-protein

Ligand binding causes GDP to be replaced by GTP on the Gα subunit.

Gαs

Stimulates adenylyl cyclase, increasing cAMP.

Gαi

Inhibits adenylyl cyclase, decreasing cAMP.

Gαq

Activates phospholipase C (PLC).

Gα12/13

Activates RhoGEFs, affecting the cytoskeleton.

cAMP production

Adenylyl cyclase converts ATP to cAMP, activated by Gαs.

cAMP degradation

Phosphodiesterase breaks cAMP down to AMP.

cAMP role in amplification

One ligand leads to multiple GPCR activations → many G-proteins → high cAMP.

targets of cAMP

PKA, ion channels, transcription factors.

phototransduction

Light activates Rhodopsin (GPCR) → Transducin (Gα) → PDE → cGMP decreases → ion channel closes.

PKA function

Phosphorylates targets leading to changes in gene expression, metabolism, ion channel activity.

glucagon pathway

GPCR → Gαs → ↑cAMP → PKA activation.

epinephrine pathway

GPCR → Gαs → ↑cAMP → PKA activation.

insulin effect on glucose levels

Via RTK and PI3K pathway → promotes glucose storage.

PKA effect on glycogen

Inhibits glycogen synthase, activates glycogen phosphorylase.

signaling diagram symbols

Boxes = proteins, arrows = activation, flat ends = inhibition.

ligand

A molecule that binds to a receptor to initiate signaling.

effector

A downstream target molecule or enzyme in a signaling pathway.

PKA

Protein kinase A, activated by cAMP.

phosphorylation

The addition of a phosphate group to a protein, altering its function.

Endocrine signaling specificity

Only target cells with specific receptors for the hormone can respond, ensuring specificity despite widespread hormone distribution.

Second messengers in GPCR pathways

Second messengers like cAMP can be produced in large quantities from a single receptor activation, enabling activation of many downstream targets and amplifying the signal.

Reversibility of phosphorylation

Phosphorylation is reversible due to the action of phosphatases. This allows dynamic regulation of protein function and ensures signals can be rapidly turned off or modulated.

Structural features of GPCRs

GPCRs have 7-transmembrane helices and an intracellular loop that undergoes conformational change upon ligand binding to interact with G-proteins.

cAMP and gene expression

cAMP activates PKA, which can translocate to the nucleus and phosphorylate transcription factors, altering gene expression.

GPCR vs RTK signaling in glucose regulation

GPCR signaling (glucagon/epinephrine) increases blood glucose by activating PKA. RTK signaling (insulin) promotes glucose uptake and storage via PI3K pathway.

Ras pathway and cancer

Mutated Ras can remain in an active GTP-bound state, continuously activating downstream pathways like MAPK, leading to uncontrolled cell proliferation.

Localization of second messengers

DAG remains membrane-bound to activate membrane-associated PKC, while IP₃ diffuses through the cytoplasm to release Ca²⁺ from the ER.

Function of arrestin in GPCR desensitization

Arrestin binds phosphorylated GPCRs to block further G-protein activation and initiate receptor internalization.

Long-term cellular changes from signaling

Through transcriptional regulation, signal transduction can alter gene expression patterns, leading to changes in protein synthesis and long-term cellular behavior.