Cell Bio Exam 3

endocrine signaling

signaling molecules are secreted by specialized endocrine cells and carried through circulation to act on target cells

paracrine signaling

signaling molecules act locally to affect behavior of nearby cells

autoctone signaling

cells respond to signaling molecules that they themselves produce

example of endocrine signaling

steroid hormone estrogen, produced by ovaries, stimulates development/maintenance of female reproductive system

example of paracrine signaling

action of neurotransmitters, carrying signals between nerve cells at synapse

example of autocrine signaling

certain T lymphocytes respond to antigenic stimulation by synthesizing a growth factor that drives their own proliferation, amplifying immune response

where are protein receptors?

either on target cell surface or intracellular (cytosol or nucleus)

how do intracellular receptors respond to signaling molecules?

when they diffuse across the plasma membrane

example of signaling molecules able to diffuse across membrane

steroid hormones

what are steroid hormones synthesized from?

cholesterol

sex steroid hormones

testosterone, estrogen, and progesterone (all from gonads)

what does the adrenal gland produce?

corticosteroids

thyroid hormone

synthesized from tyrosine in thyroid gland, development and regulation of metabolism

Vitamin D3

regulates Ca2+ metabolism and bone growth

retinoic acid

synthesized from vitamin A, important roles in vertebrate development

how do thyroid hormones cross plasma membrane

facilitated by carrier proteins; once inside they bind to intracellular receptors

what is the family of proteins the receptors the thyroid hormones bind to?

nuclear receptor superfamily; TFs that contain related domains for ligand binding, DNA binding, and transcriptional activation

another molecule that can transmit signals between cells?

nitric oxide (NO)

what does NO do?

diffuses across plasma membrane and signals dilation of blood vessels, increasing blood flow

what is different about NO once it passes membrane?

it doesn’t bind to a receptor, it alters activity of guanylyl cyclade to stimulate cyclic GMP synthesis

neurotransmitters

carry signals between or from neurons to other types of target cells; small and hydrophilic

what is release of neurotransmitter signaled by?

arrival of action potential at terminus of a neuron

examples of neurotransmitters

glutamate, acetylcholine, and gamma-aminobutyric acid (GABA)

what do neurotransmitters diffuse across?

synaptic cleft

what do neurotransmitters bind to?

because they are hydrophilic, they bind to cell surface receptors!

many are ligand-gated ion channels, binding induces a conformational change, and some are G protein coupled

what do plant hormones do?

regulate plant development and growth; modified by environmental factors

auxin

one of the first plant hormones discovered, induces plant cell elongation by weakening the cell wall

gibberellins

plant hormones for stem elongations

ethylene

plant hormone for fruit ripening

cytokinins

plant hormone for cell division

abscisic acid

plant hormone for onset of dormancy

widest variety of signaling molecules in animals

peptides (peptide hormones, neuropeptides, and polypeptide growth factors)

peptide hormones

insulin and pituitary gland hormones (growth hormone, follicle-stimulating hormones, prolactin, and others)

neuropeptides

enkephalins and endorphins, decrease pain response in CNS

polypeptide growth factors

signaling molecules that control animal cell growth and differentiation

nerve growth factor (NGF)

regulate development and survival of neurons

epidermal growth factor (EGF)

stimulates cell proliferation

platelet-derived growth factor (PDGF)

stimulates proliferation and movement of fibroblasts in vicinity of wound/clot; also helps in devo of embryonic tissues

cytokines

another type of polypeptide growth factor, regulates devo and differentiation of blood cells, and crontrols activities of lymphocytes during immune response

what do other polypeptide growth factors do/are located?

(ex. membrane-anchored growth factors) remain in membrane, not secreted, function during direct cell-cell interactions

what receptors do peptide hormones, neuropeptides, and growth factors bind to?

cell surface receptors, they cannot cross membrane of target cells

signal transduction

process where enzymes transmit signals from the receptor to a series of additional intracellular targets

G proteins

largest family of cell surface receptors that transmits signals to intracellular targets via intermediary action of guanine nucleotide-binding proteins

G protein coupled receptors

the cell surface receptors with a G protein

characterized by seven membrane-spanning alpha helices, an extracellular ligand-binding domain, and an intracellular domain with a guanine nucleotide-exchange factor (GEF)

what is the process after ligan dis bound of G protein coupled receptor?

ligand binding induces conformational change, cytosolic domain activates G protein, G protein dissociates from receptor and carries signal to intracellular target

absence of hormone (glucocorticoid signaling)

receptor associates with co-depressors with HDAC activity → gene expression repressed

hormone present (glucocorticoid signaling)

hormone binds receptor, conformational change, co depressor is displaced, association w co factors w HAT activity → transcription activated

nitroglycerine for heart disease

converts to NO which dilates blood vessels and increases blood flow to heart

what do carbohydrates do on G proteins?

required for proper folding

adenyl cyclase

enzyme responsible for cAMP formation

steps leading up to adenyl cyclase activation

1. hormone (epinephrine) binds to extracellular domain of receptor

2. binding causes conformation change, activating G protein

3. g protein dissociates and carries signal to intracellular target

4. binds to adenyl cyclase enzyme and creates cAMP

G proteins and cyclic AMP in absence of hormone

G protein coupled receptor is inactive, the alpha subunit is bound to GDP w beta and gamma

G protein and cyclic AMP in presence of hormone

1. hormone binds extracellular domain of G protein coupled receptor

2. activated receptor acts as GEF

3. binding of hormone stimulates release of GDP

4. GDP is exchanged for GTP

when is the G protein active?

when GTP is bound to alpha subunit

G proteins and cyclic AMP when G protein is activated

activated alpha beta gamma complex dissociate from receptor and goes to interact with targets

what does cholera toxin do?

inhibits ability of alpha subunit of Gs to hydrolyze GTP → adenyl cyclase always on, cAMP always made

protein kinase A (PKA)

tetramer consisting of two regulatory and two catalytic subunits (inactive state)

glycogen breakdown steps

1. epinephrine stimulates adenyl cyclase to synthesize cAMP

2. cAMP binds to regulatory subunits of PKA

3. conformational change induced, catalytic subunits dissociate

4. catalytic subunits are active, phosphorylate serine residues in target proteins

5. catalytic subunit phosphorylates phosphorylase kinase, whinxh in turn phosphorylates glycogen phosphorylase

6. glycogen phosphorylase catalyzes breakdown of glycogen to glucose-1-phosphate

cyclic amp inducible gene steps

1. signal leads to activation of the catalytic domain of PKA

2. signal translocates from cytoplasm to nucleus

3. PKA catalytic unit phosphorylates CRE-binding protein (CREB) a TF

4. co factor binds CREB

5. transcription of cAMP-inducible genes

what do kinases do

phosphorylate

what do phosphatases do

de-phosphorylate

structure of a receptor tyrosine kinase

N-terminal extracellular ligand binding domain, single transmembrane alpha helix, cytosolic C-terminal with tyrosine kinase activity

receptor tyrosine kinase signaling

1. growth factor binds to ligand binding domain

2. receptor dimerization induced

3. autophosphorylation of receptors and two polypeptide chains cross-phosphorylate each other

non receptor tyrosine kinase signaling

1. cytokine binds to ligand

2. receptor dimerization induced

3. cross phosphorylation of nonreceptor kinases

4. phosphorylation of receptor (the tyrosine residues of it)

MAP kinase signaling

major pathways of signal transduction, activated downstream of both receptor and non receptor tyrosine kinases

what is Ras protein

causes sarcoma in rats

when active, directly influences proliferation of normal mammalian cells

what happens when Ras is interfered with?

blocks growth factor induced cell proliferation

how is Ras regulated

GEFs release GDP for GTP, when Ras is bound to GTP its active. Activity is terminated by GAPs by hydrolyzing GTP

PI 3 kinase pathway

1. PI 3 kinase is recruited by its SH2 domain to activated receptor tyrosine kinases

2. PI 3 kinase converts PIP2 into PIP3

3. PIP3 binds to Akt and Akt recruited to plasma membrane

4. Akt phosphorylated and activated by PDK1 and mTORC2 (which also bind to PIP3) so now they’re all on the plasma membrane

5. when they’re all associated with plasma membrane Akt is phosphorylated and activated!!!!

what does Akt activating lead to?

regulation of FOXO-induced genes, mTOR, GSK, and Bad

TGF-beta/Smad pathway

1. TGF-b receptors have two polypeptides (type I and type II)

2. type II phosphorylates type I

3. Smad phosphorylate

4. Smad forms complexes and translocates to nucleus to activate transcription of target genes

what is different about TGF-b receptors?

they are kinases that phosphorylate serine or threonine not tyrosine

tumor necrosis factor, TNF

cytokine that induces inflammation and cell death