Citterio Exam 3 (Mostly Review Session)

These flashcards cover key concepts related to signal transduction and hormonal action, focusing on definitions, processes, and mechanisms involved.

Signal transduction is the transmission of ______________ from a cell’s ________ to its _______.

molecular signals, exterior, interior

Types of signals involved in signal transduction include:

Antigens, hormones, neurotransmitters, light, touch, and pheromones

These transduction signals cause changes in the cell:

• __________ and __________

• Gene __________ and _______

• Change in an ____________, etc.

Differentiation, cell division, transcription, translation, enzymatic activity

Biological importance of Signal Transduction:

• All cells have ______ and __________ signal-transducing mechanisms, which have been ________ during evolution.

• ____________ of the production and ______ of hormones and other regulatory signaling molecules is a major cause of ________.

specific, highly sensitive, conserved, dysregulation, release, disease

Receptors are membrane-bound or soluble proteins that exert a physiological effect after binding their ___________.

natural ligand

Binding interactions are:

• ________ and ________

• ________

• ______ and ______ states

• _______

Target cell response depends on:

• Ligand ________ at the receptor

• __________ specific factors

specific, sensitive, reversible, active, inactive, saturable, concentration, target cell

Specificity in signal transduction refers to the _________ of a signaling ______ to its _____________ receptor.

binding, ligand, complementary

Explain the general sequence of events involved in signal transduction.

Reception, Transduction, Response, and End

• Reception: A _______ interacts with a _________

• Transduction: The _________ receptor interacts with _______ machinery

• Response: A ____ signal is produced, or the activity of a _______ is altered, modifying the activity/behavior of the _________.

• End: __________ event ends

ligand, receptor, activated, cellular, 2nd, protein, target cell, transduction

In amplification, when enzymes activate enzymes, the number of affected molecules ________ in an enzyme ________.

increases geometrically, cascade

Describe general features of signal transduction systems.

Specificity, amplification, desensitization, and integration

1. Specificity: _____________ first binding site on its ___________ receptor; other ligands ______ fit

2. Amplification: when enzymes _________ enzymes, the number of affected molecules ______ geometrically in an enzyme _________

3. Desensitization/Adaptation: receptor activation triggers a _________ circuit that ________ the receptor or ________ it from the cell _______

4. Integration: when 2 signals have ________ effects on a metabolic characteristic, such as the ________ of a ___ messenger X, or the _____________ Vmax, the regulatory outcome results from the integrated input from ____ receptors

signaling ligand, complementary, do not, activate, increases, cascade, feedback, shuts off, removes, surface, opposite, concentration, 2nd, membrane potential, both

Signal transduction often involves a _____________ feedback circuit that shuts off the receptor or removes it from the cell surface.

desensitization/adaptation

Explain the classification of signal-transduction systems according to the receptor type and signaling mechanism.

1. Nuclear Receptor: _______ binding allows the receptor to regulate the expression of specific _____ (Group _ hormones.)

2. G protein-coupled receptor (GPCRs): External ligand binding to a receptor activates an intracellular GTP-binding protein, which regulates an enzyme that generates an _________________ (Group _ hormones)

3. Receptor enzyme (__): ligand binding activates activity by _________________→ ______ activates ___________ factor, altering gene expression (Group _ hormones, ______, ______ factors, _________

4. Gated ion channel: channel opens/closes in response to the __________ of the signal ______ or the ________________ (not activated by __________)

hormone, genes, I, intracellular 2nd messenger, II, TK, autophosphorylation, kinase, transcription, II, cytokines, growth, interleukins, concentration, ligand, membrane potential, hormones

Group I hormones bind to ________ receptors and affect gene expression.

• Receptors can be located in the ______ (e.g. gluco-corticoids) or in the _______ (e.g. thyroid hormone)

• Cytosolic hormone-receptor complexes are translocated into the _______.

• Once in the nucleus, the hormone-receptor complex binds to a ______________________ associated with a specific ___ sequence and acts as a _____________ factor.

• The HRE may have up to __ proteins acting as coregulators and coactivators of gene transcription

intracellular, cytosol, nucleus, nucleus, hormone response element (HRE), DNA, transcription, 30

Three essential components define signal transduction through GPCRs:

1. a ___________________ with seven transmembrane helical segments,

2. a _______ that cycles between active (___-bound) and inactive (___-bound) forms, serving as the coupler, or transducer of the signal. The subunits of the heterotrimeric G-proteins are called the α, β, and γ subunits.

3. an ___________ (or ion channel) in the plasma membrane that is regulated by the activated G protein and produces the ____________.

plasma membrane receptor, G protein, GTP, GDP, effector enzyme, 2nd messenger

Cyclic GMP is generated by the enzyme ________, which can exist in soluble and membrane-bound forms.

guanylyl cyclase

Many Group _ hormones, such as epinephrine, bind to cell surface receptors that generate intracellular second messengers like ____ and _____.

II, cAMP, cGMP

The process of signal transduction through _______________ involves three essential components: a ______________ receptor, a ________, and an _______ enzyme.

G protein-coupled receptors, plasma membrane, G protein, effector

_________ hormones binding to Receptors in ___ → Release of __________ → ______________

Receptors bound to ___

hydrophobic, TRE, compressors, DNA transcription, TRE

Upon ligand binding, receptor tyrosine kinases ________, leading to the activation of __________- signaling pathways.

autophosphorylate, intracellular

The JAK/STAT pathway involves Janus kinase (JAK) and signal transducers (STATs) that translocate into the _______ to activate ___________.

nucleus, transcription

NF-κB is sequestered in the cytosol by an _________ protein known as ___.

inhibitory, IkB

_________ regulates the NF-κB pathway by inhibiting its activation and subsequent __________________.

Cortisol, gene transcription

Hydrolysis of cAMP to 5'-AMP is catalyzed by _____________, which can terminate the signal transduction response.

phosphodiesterases

Drug interventions affecting signaling can include receptor modulation, enzyme inhibition, and __________________.

second messenger regulation

Many Group _ hormones activate GPCRs

• There are many ___-binding proteins

• __, __, __, G12, Go

• ______ number of subtypes

II, GTP, Gs, Gi, Gq, large

Many different effector systems

• ____________ (9 isoforms)

  • Second messenger cAMP

• __________________

  • Second messenger diacylglycerol and inositol triphosphate

• _______ and ____________

  • Second messenger calcium/potassium

• ______________

  • Second messenger cGMP

Adenyl cyclase, Phospholipase C, Calcium, potassium channels, Guanylate cyclase

• A hormone (ligand) binds to a _____ on the cell membrane. This activates a _______, which in turn activates ______________ (PLC)

• ___ acts on a membrane phospholipid called phosphatidylinositol 4,5-bisphosphate (____).  ____ is cleaved into two important second messengers: Inositol trisphosphate (___) and Diacylglycerol (___)

• ___ releases Ca²⁺ from the __

• Ca²⁺ binds to _________

• DAG activates ____________ (PKC)

• The combination of ___ activation and ______________ signaling modifies the activity of numerous proteins

GPCR, G protein, phospholipase C, PLC, PIP2, PIP2, IP3, DAG, IP3, ER, calmodulin, Protein kinase C, PKC, Calcium/calmodulin, 

• AC → ____ (___ messenger) from ATP → bind to subunits of ___ → releases the _______ part of ___ and makes it ______

cAMP, 2nd, PKA, catalytic, PKA, active

Gs: Epinephrine

• Epinephrine binds to _________ receptor → allosteric change in hormone-receptor complex causes ___ bound to ______ to be replaced by ___ → activates _______, then separates to activate __ → AC catalyzes ____→ cAMP activates → ___ → _____________ of cellular proteins by ___ causes cellular response to epinephrine → cAMP is _______, reversing ___ activation

Beta-Adrenergic, GDP, Gs-alpha, GTP, Gs-alpha, AC, cAMP, PKA, phosphorylation, PKA, degraded, PKA

____________ is the process by which a small signal (1 molecule of epinephrine) is greatly increased in magnitude in a signaling cascade (lots of blood glucose molecules).

Amplification

Several Mechanisms Cause Termination of the β-Adrenergic Response

• __________ of epinephrine in the blood drops.

• ________ of ___ bound to the ______ subunit, catalyzed by the intrinsic GTPase activity of the G protein.

• _________ of ____ to 5′-___ (not active as a second messenger)

• _________________________ reverse effects of PKA

Concentration, hydrolysis, GTP, G-alpha, hydrolyses, cAMP, AMP, Phosphoprotein phosphatases

_____________ is the reduction in responsiveness of the receptor to its ligand after prolonged exposure.

Epinephrine bound to ___________ receptors → triggers dissociation of ___________ from Gs-alpha → Gs-beta-gamma recruits ________ to the membrane → _________ Ser residues at the ____________ of the receptor → _________ (Beta-arr) binds to the phosphorylated carboxyl-terminal domain of the receptor → Receptor arrestin complex enters the cell by ________ → ______ dissociates → receptor is ____________ → returns to cell surface

Desensitization, beta-adrenergic, Gs-beta-gamma, Beta-ARK, phosphorylates, carboxyl terminus, Beta-arrestin, endocytosis, arrestin, dephosphorylated

STUDY

STUDY

Features of Insulin Action:

• Insulin is released from ____ cells in pancreas when blood glucose levels are ____.

• When insulin binds to receptors, an intrinsic ______________________. This recruits __________________ (IRS) which are also phosphorylated and activated.

• ___ activate a variety of proteins initiating kinase cascades

• Protein kinase _ → increases glycogen synthesis and glucose uptake

• ___ and ___ kinase → cell growth and gene transcription

Beta, high, tyrosine kinase autophosphorylates, insulin receptor substrate proteins, IRS, B, MEK, MAP

STUDY

Regulation of Gene Expression by insulin through MAP protein kinase cascade

_____ binds to receptor → ____________ IRS-1 on Tyr residues → _______ of IRS-1 binds to mediator proteins → binding to ___ causes ___ release and ___ binding to ___ → activated Ras binds and activates _____ → Raf-1 phosphorylates ___ and _______ it → MEK phosphorylates __________ (on Thr and Tyr residue) and activates it → ____________ moves into the nucleus and __________ nuclear transcirption factors (_____) and activates them → _________________ joins SRF to stimulate transcription and translation genes for cell division

Insulin, autophosphorylates, Phosphate, Ras, GDP, GTP, Ras, Raf-1, MEK, activates, ERK/MAP kinase, ERK/MAP kinase, phosphorylates, Elk-1, phosphorylated Elk1

STUDY

Understand the patterns of signal transduction and pathway crosstalk in mediating physiological processes

• Insulin receptor ________ → releases ___ (phosphorylate of β-Adrenergic receptor) → ____ internalization/desenstiization (reduced GPCR responsivness) → leads to recruitment of _______________ (SHC, Grb2, Sos, Ras, Raf-1) → activated ___ → ___ → alter _______________

activated, PKB, GPCR, mediator proteins, MEK, ERK, gene expression

• _____ receptor → activates ___ → ___

• ___ receptor activation → ___

• PKA → phosphorylates _______ → goes to the ______ and alters gene transcription (cell __________ and cell _____________)

IGF-1, Akt, PKA, TSH, PKA, beta-cat, nucleus, proliferation, differentiation

JAK/STAT pathway is used by hormones and cytokines:

• Some hormones (e.g. _____ hormone) and the ______ activate a __________ that is ___ an integral part of the ______ receptor.

• ___________ (JAK) is associated with, but not part of, the ______________ hormone receptor

• Upon ligand binding, receptors _____ which activates ___

• JAK ____________ the receptor attracting proteins called ______ (signal transducers and activators of transcription)

• ____________________ dimerize and translocate into the nucleus where they bind to ____________ and activate transcription.

• The phosphotyrosine residues of the receptor also activate proteins of the __________ pathway as well as G protein- mediated activation of ___ demonstrating “__________.

growth, cytokines, tyrosine kinase, not, hormone, Janus kinase, cell surface growth, dimerize, JAK, phosphorylates, STATs, Phosphorylated STATs, response elements, MAP kinase, PLC, cross-talk

STUDY

NF-κB pathway:

__________ RESPONSE

• ___ phosphorylated to ___ and ___ and activate transcription that leads to inflammation, regulated by ___________

INFLAMMATORY, IkB, p50, p65, glucocorticoids

The NF-κB Pathway is regulated by Glucocorticoids:

• The anti-inflammatory and immunomodulatory action of _______ are explained in part by a 3-fold inhibition of _____ pathway.

  • _______ increases _______ and therefore IκB protein and more efficient sequestration of NF-κB in the ________.

  • The ____________ receptor competes with NF-κB for binding to _________

  • The glucocorticoid receptor directly binds to the ___ subunit of NF-κB and ______ its action.

cortisol, NF-kB, Cortisol, IkB mRNA, cytoplasm, glucocorticoid, coactivators, p65, inhibits

Development of Protein Kinase Inhibitors for Cancer Treatment

• In all types of cancer, the normal regulation of cell division has become __________ due to defects in one or more genes such as ____________

• The simplest protein kinase inhibitors are _________ that occupy the ATP binding site but cannot serve as ___________________

• For example, _______, which targets ____, is effective against advanced ____________________ (NSCLC)

dysfunctional, protein kinases, ATP analogs, phosphoryl group donors, Erlotinib, EGFR, non-small cell lung cancer