Cell and Molecular Biology Lecture 9: Cellular Receptors - Signal Transduction

What is the movement of signals from outside the cell to the inside?

Signal transduction

What are the three stages of signal transduction?

Reception, transduction, cellular response

What is the signaling mechanism that features a hormone entering the bloodstream and reaching a receptor on a target cell?

Endocrine

What is the signaling mechanism that features a signaling cell using a local mediator to send a signal to local target cells?

Paracrine

What is the signaling mechanism that uses neurotransmitters?

Neuronal/Synaptic

What is the signaling mechanism that requires a membrane-bound signal molecule coming into direct contact with the target cell's receptor?

Contact-Dependent

What are the 6 hormonal signaling molecules?

Cortisol, estradiol, glucagon, insulin, testosterone, thyroid Hormone

What are the 4 growth factors?

EGF, NGF, PDGF, TGF-beta

What are the 2 local mediators?

Nitric Oxide and Histamine

What are the 2 neurotransmitters?

Acetylcholine and gamma-Aminobutyric acid (GABA)

What are the 4 extracellular matrix proteins?

Collagen, Osteopontin, Fibronectin, Vitronectin

What are the receptors that are found inside the cytoplasm or the nucleus of a cell and utilize a hydrophobic signal molecule?

Intracellular receptors

What are the receptors that are found on the surface of the cell and utilize a hydrophilic signal molecule?

Cell-surface receptors

Most receptors are what type of receptors?

Cell-surface

What are the 4 examples of cell-surface receptors?

Ion-channel, G-protein linked, Enzyme-linked, Integrin

What are the 5 examples of intracellular receptors?

Cortisol, Estradiol, Testosterone, Thyroxine, Vitamin D3

Which intracellular receptors are present in the cytoplasm?

Glucocorticoids and Mineralocorticoids

Which intracellular receptors are present in the nucleus?

Estrogen, Androgen, Progesterone, Thyroid Hormone, and Vitamin D

Ligand binding causes what type of change in the structure of the channel protein that leads to the opening of the channel gate?

Conformational change

What are 2 examples of ion-channel coupled receptors?

Acetycholine and NMDA

What are the largest family of membrane proteins in the human genome?

G-Protein coupled receptors

How many transmembrane domains do G-Protein coupled receptors have?

7

What subunits do G-Protein coupled receptors have?

Alpha, beta, and gamma

Which G-Protein coupled receptor subunit(s) is/are GTP bound?

Alpha

What are receptors with intrinsic kinase activity and autophosphorylate themselves and phosphorylate downstream signaling molecules?

Receptor kinases

TGF-beta receptors are examples of which type of receptor kinases?

Serine-threonine

PDGFR and EGFR are examples of which type of receptor kinases?

Tyrosine

The binding of the ligand to the receptor causes _____ to phosphorylate and activate each other

Tyrosine kinases

What are heterodimeric receptors with an alpha and a beta chain and no kinase activity?

Integrin receptors

Which ligands correspond to integrin receptors?

Collagen, Laminin, Fibronectin, and Vitronectin

What adds a phosphate group to a Tyr or Ser-Thr containing protein?

Kinase

What removes a phosphate by hydrolysis?

Phosphatase

What is the family of proteins that are activated by the binding of GTP and inactivated by the hydrolysis of GTP to GDP?

Rho GTPases

What facilitates the formation of appropriate signaling complexes within a cell during signal transduction?

Adaptor proteins

Complex interactions between signaling proteins are mediated by _____

Modular domains

_____ and _____ were first identified in Src kinase

SH2, SH3

_____ Homology domains 2 and 3 are also known as SH2 and SH3

Src

SH2 domains bind to short phosphorylated _____-containing sequences

Tyrosine

SH3 domains bind to _____-rich sequences

Proline

SH2 and SH3 domains are potential targets for anti-_____ drugs

Cancer

What are non-protein substances that are enzymatically generated through receptor activation in the cell?

Second Messengers

What are the 5 second messengers?

cAMP, cGMP, Lipids (Phosphoinositides and DAG), Ca2+, and NO

What is one of the best characterized second messengers?

cAMP

What is the family of enzymes that depends on cAMP?

PKA

What is a hypomineralization disorder caused by excessive ingestion of fluoride during early childhood?

Dental Fluorosis

What regulates enamelin?

Casein kinases

What regulates mineralization?

Alkaline phosphatases

Fluoride alters casein kinase II and alkaline phosphatase in _____

Ameloblasts

_____ reduces the function of Rho GTPases and osetoclasts

Bisphosphonates (BPs)

_____ is a rare complication and is developed with high-dose therapy with BPs

Osteonecrosis of Jaw (ONJ)

What is the mechanism by which BPs cause ONJ?

Unknown