Chapter 16: Cell Signaling

direct cell-cell signaling

direct interaction of a cell with its neighbor

signaling by secreted molecules

endocrine signaling, paracrine signaling, autocrine signaling

transmembrane proteins involved in direct cell-cell signaling

integrins, cadherins

endocrine signaling

carried through circulation to target cells at distant body sites, secreted by specialized endocrine cells

example of endocrine signaling

estrogen

paracrine signaling

released by one cell to act on neighboring target cells (doesn’t require physical contact)

example of paracrine signaling

neurotransmitters

autocrine signaling

cells respond to signaling molecules that they produced themselves

example of autocrine signaling

T lymphocytes respond to antigens by making a growth factor that drives their own proliferation

intracellular receptors

respond to small hydrophobic molecules that can diffuse across the plasma membrane (hormones, lipids)

cholesterol

synthesizes steroid hormones

sex steroids produced by the gonads

testosterone, estrogen, and progesterone

steroid hormones produced from the adrenal gland

corticosteroids (glucocorticoids, mineralocorticoids)

hormone synthesized by tyrosine in the thyroid gland

thyroid hormone

regulates Ca²⁺ metabolism and bone growth

vitamin D₃

synthesized from vitamin A

retinoic acid and retinoids

receptors for steroid hormones/lipids

members of the nuclear receptor superfamily

structure of nuclear receptors

transcription factors with domains for ligand binding, DNA binding, and transcriptional activation

glucocorticoid receptor when in the absence of glucocorticoid

bound to Hsp90 chaperones

result of glucocorticoid binding to its receptor

displaces Hsp90 which leads to the binding of regulatory DNA sequences

thyroid hormone receptor when in the absence of thyroid hormone

associated with a compressor complex to repress transcription of target genes

result of thyroid hormone binding to its receptor

transcription activation

nitric oxide (NO)

very small paracrine signaling molecule in the nervous, immune, and circulatory systems

nitric oxide transport across the plasma membrane

direct diffusion

main target of nitric oxide

guanylyl cyclase

result of nitric oxide binding to guanylyl cyclase

stimulates synthesis of cyclic GMP by diffusing to smooth muscle cells

cyclic GMP function

induced muscle cell relaxation and blood vessel dilation (increases volume flow, reduces blood pressure)

neurotransmitter receptors

ligand-gated ion channels, G proteins

neurotransmitter transport across the plasma membrane

hydrophilic and can’t cross the membrane; must bind to cell surface receptors

peptide signaling molecules

peptide hormones, neuropeptides, polypeptide growth factors

peptide hormones

insulin, glucagon, pituitary gland hormones

neuropeptides

secreted by some neurons

cytokines

regulate development and differentiation of blood cells and activities of lymphocytes during the immune response

membrane-anchored growth factors

remain associated with the plasma membrane and function as signaling molecules in direct cell-cell interactions

intracellular signal transduction

surface receptors regulate intracellular enzymes which triggers an intracellular signal cascade

structure of G protein-coupled receptors

7 membrane-spanning α-helices, GEF domain inside the cell, ligand-binding domain outside of the cell

result of a primary messenger (hormone) binding a ligand

conformational change in the cytosolic domain activates a G protein

result of G protein activation

the G protein disassociates from the receptor and carries the signal to its intracellular target

result of activated G protein reaching the intracellular target

activation of adenylyl cyclase synthesizes cAMP

state of G protein bound to GDP

inactive state

state of G protein bound to GTP

activated state

portion of the G protein that disassociates

α-subunit bound to GTP

subunits of G proteins

α subunit, ß subunit, γ subunit

molecule that degrades cAMP to AMP

cAMP phosphodiesterase

molecule that forms cAMP from ATP

adenylyl cyclase

structure of inactive protein kinase A

2 regulatory subunits and 2 catalytic subunits

function of protein kinase A

binds cAMP, which frees the catalytic subunit, allowing it to phosphorylate CREB

CREB

transcription factor that is phosphorylated by protein kinase A to start transcription

receptor tyrosine kinases

has receptors for most polypeptide growth factors

result of a growth factor binding to a receptor tyrosine kinase

dimerization of the receptor

result of receptor dimerization (in receptor tyrosine kinases)

receptor autophosphorylation (the two polypeptide chains cross-phosphorylate each other)

result of receptor autophosphorylation (in receptor tyrosine kinases)

the downstream signaling molecule SH2 can bind to the activated receptor

non-receptor tyrosine kinases

functionally equivalent to receptor tyrosine kinases

MAP kinase pathway

major pathway of signal transduction that maintains cell survival and proliferation

ERK family

kinase family to which MAP kinases belong

function of GEF

activates RAS by phosphorylating GDP to GTP

function of GAP

terminates RAS-GTP activity (inactivates it)

result of RAS activation

activation of RAF protein

result of RAF activation

phosphorylation and activation of MEK (MAP/ERK kinase)

result of MEK activation

activation of ERK to regulate transcription

result of the second MAP kinase pathway (response to cell stress)

inflammation, cell death

scaffold proteins

allow molecules to interact easily through physical association

PI 3-kinase/Akt pathway

results in regulation of gene transcription, regulation of metabolism, and induces cell survival (inhibition of Bad)

PIP₂

2nd messenger that is phosphorylated by PI 3-kinase

result of PIP₂ phosphorylation

production of PIP₃

PIP₃ function

targets the serine/threonine kinase Akt for phosphorylation