Hormone Transport, Receptors, Signal Transduction (3A) - MCAT Biological and Biochemical Foundations of Living Systems

Cell signals itself via its own receptors. Autocrine signaling enables self-regulation where a cell produces and responds to its own signaling molecules, often in growth or immune responses.

Contact-dependent signaling between adjacent cells. Juxtacrine signaling requires direct physical contact, facilitating precise communication in developmental processes like cell fate determination.

Neuron releases neurotransmitter into synaptic cleft. Synaptic signaling ensures rapid, targeted transmission across synapses, crucial for neural communication and reflex actions.

cAMP from ATP. Adenylyl cyclase catalyzes the conversion of ATP to cAMP, which acts as a second messenger to amplify GPCR signals intracellularly.

$IP_3$ and DAG. Phospholipase C hydrolyzes $PIP_2$ into $IP_3$ and DAG, generating dual second messengers for calcium release and kinase activation.

Opens ER $Ca^{2+}$ channels to raise cytosolic $Ca^{2+}$. $IP_3$ binds to receptors on the endoplasmic reticulum, triggering calcium release that modulates various cellular processes like contraction or secretion.

Activates protein kinase C (PKC). DAG remains membrane-bound and, with calcium, recruits and activates PKC to phosphorylate targets in signal transduction pathways.

Local mediator acts on nearby cells. Paracrine signals diffuse locally to affect neighboring cells without entering the bloodstream, allowing targeted regulation in tissues.

Endocrine signals travel via blood to distant targets. Endocrine signaling involves hormone release into the bloodstream for systemic distribution, unlike paracrine which is limited to diffusion over short distances.

Cell-surface (plasma membrane) receptors. Peptide hormones are hydrophilic and cannot cross the membrane, so they bind extracellular receptors to initiate intracellular signaling cascades.

Intracellular receptors in cytosol and/or nucleus. Steroid hormones are lipophilic and can diffuse through the plasma membrane to bind receptors inside the cell, enabling direct genomic regulation.

$G_q$. $G_q$ triggers phospholipase C to cleave $PIP_2$, initiating the $IP_3$/DAG pathway for calcium-mediated responses.

Phosphodiesterase degrades cAMP to AMP. Phosphodiesterase enzymes rapidly hydrolyze cAMP, preventing prolonged signaling and allowing precise control of cellular responses.

Ligand-induced dimerization and trans-autophosphorylation. Ligand binding promotes RTK dimerization, enabling cross-phosphorylation that creates docking sites for signaling molecules.

Docking of SH2/PTB proteins to initiate kinase cascades. Phosphotyrosine residues on activated RTKs recruit SH2/PTB domain proteins, which propagate signals through pathways like MAPK for cell growth.

Steroid hormones. Steroid hormones induce genomic effects via transcription, leading to sustained protein synthesis and longer-lasting physiological changes compared to rapid peptide actions.

Increases half-life by reducing filtration and metabolism. Binding to plasma proteins protects steroid hormones from rapid renal filtration and enzymatic degradation, thereby prolonging their presence in circulation.

Peptides circulate mostly free; steroids are carrier protein-bound. Peptide hormones are water-soluble and dissolve freely in plasma, while steroid hormones are lipid-soluble and require binding to proteins for solubility and transport.

Ligand binding directly opens or closes an ion pore. These receptors function as ion channels where ligand binding induces conformational changes to regulate ion flux and membrane potential.

Ligand-bound receptor binds DNA to regulate transcription. Steroid receptors, upon ligand binding, translocate to the nucleus and act as transcription factors to modulate gene expression.

$G_s$. $G_s$ stimulates adenylyl cyclase upon activation, increasing cAMP levels to promote downstream effects like glycogenolysis.

Receptor tyrosine kinase (RTK). The insulin receptor undergoes ligand-induced autophosphorylation, initiating cascades for glucose uptake and metabolism regulation.