physiology unit one pathways

Lipid-soluble hormone pathway

Think: cross membrane and change gene expression.

Steroid or thyroid hormone diffuses through the membrane → binds a receptor in the cytosol or nucleus → hormone-receptor complex binds DNA → transcription → mRNA → new protein → cellular response.

So if a question says the messenger crosses the membrane and eventually changes transcription, this is the one.

Ligand-gated ion channel

Think: fastest and simplest membrane pathway.

Messenger binds directly to a receptor that is itself an ion channel → channel opens → ions move → cellular response.

No long second-messenger cascade is needed.

Receptor tyrosine kinase

Think: dimerize and phosphorylate tyrosines.

Messenger binds → two receptors dimerize → kinase portions activate → receptors cross-phosphorylate → relay proteins bind → relay proteins are phosphorylated → effector protein changes → response.

Shortcut:

RTK = receptor itself is the kinase

That distinction matters when you compare it with JAK-STAT.

Enzyme-coupled receptor / JAK-STAT

Think: receptor and enzyme are separate proteins.

Messenger binds → receptors dimerize → associated JAK enzymes activate → JAKs phosphorylate receptor sites → STAT proteins dock and get phosphorylated → STAT enters nucleus → binds DNA → transcription → effector protein → response.

This is the easiest way to separate it from RTK:

RTK: receptor itself has kinase activity.
JAK-STAT: kinase is a separate protein attached to the receptor.

Guanylyl cyclase receptor

Think: cGMP pathway.

Messenger binds → receptor dimerizes → guanylyl cyclase activates → GTP becomes cGMP → cGMP activates PKG → PKG phosphorylates an effector protein → response.

Memorize:

GC → cGMP → PKG

That three-part chain is the identity of this pathway.

GPCR — cAMP pathway

Messenger → GPCR → Gs → adenylyl cyclase → ATP becomes cAMP → cAMP activates PKA → PKA phosphorylates effector protein → response.

Memorize this exact chain:

Gs → adenylyl cyclase → cAMP → PKA

If you see cAMP, think PKA.

And if you see adenylyl cyclase, think cAMP.

GPCR — IP₃/DAG pathway

Messenger → GPCR → Gq → phospholipase C → membrane phospholipid is split into IP₃ + DAG → IP₃ goes to ER → opens channels → Ca²⁺ enters cytosol → DAG + Ca²⁺ activate PKC → phosphorylation → response.

Memorize:

Gq → PLC → IP₃ + DAG → Ca²⁺ → PKC

Compare it directly with the other GPCR:

Gs → adenylyl cyclase → cAMP → PKA

Gq → phospholipase C → IP₃/DAG → Ca²⁺ → PKC

That comparison is probably the single most useful thing to memorize from the signaling section.

Nitric oxide

NO diffuses through the membrane → binds an intracellular receptor → activates guanylyl cyclase → GTP becomes cGMP → cGMP activates PKG → PKG phosphorylates an effector protein.

So nitric oxide also uses:

cGMP → PKG

But unlike the membrane guanylyl cyclase receptor pathway, NO itself crosses the membrane.