Signaling III

Question 1

Epidermal Growth Factor Receptor (EGFR)

Answer 1

a membrane-bound receptor tyrosine kinase (RTK) that dimerizes upon binding its hormone - Epidermal Growth Factor (EGF). Dimerization is necessary for RTK activation. RTKs play important roles in regulating cell proliferation.

Question 2

Dimerization of EGFR

Answer 2

results in autophosphorylation of its cytoplasmic tails, which are targets for binding by a signaling complex. The bound signaling complex acts to activate a protein known as RAS by causing it to release GDP and replace it with GTP. RAS is like the alpha subunit of a G-protein. It binds to guanine nucleotides. When bound to GDP, it is inactive and when it binds to GTP, it is activated.

Question 3

Activation of RAS

Answer 3

results in activation of transcription pathways that result in cell division.

Question 4

RAS

Answer 4

acts by activating a kinase cascade that ultimately activates transcription of genes necessary for cell division.

Question 5

Turning off EGFR signaling involves

Answer 5

the GTPase activity of RAS, phosphatases, and endocytosis of receptors.

Question 6

Steroid hormone signaling

Answer 6

does not require membrane receptors, since steroid hormones can move across membranes by themselves, for the most part, though vitamin D has a membrane receptor that factilitates its movement across the membrane.

Question 7

Steroid hormones affect

Answer 7

cellular metabolism, inflammation, immune functions, water/salt balance, sexual characteristics, and response to illness/injury

Question 8

Signaling by steroid hormones involves

Answer 8

1) binding to a receptor in the cytoplasm or nucleus; 2) conformational change of the receptor on binding; 3) entry into the nucleus (if it isn’t already there); and 4) binding to DNA to affect transcription.

Question 9

Nerve transmission

Answer 9

a signaling system noted for its rapidity (millisecond responses). It operates by using ion gradients and neurotransmitters to communicate information quickly. Ion channel blockers can stop nerve transmission.

Question 10

Prostanoids (prostaglandins)

Answer 10

hormone-like molecules that have numerous functions. One of these is localized pain (bee stings / headaches). Prostanoid production is inhibited by aspirin and ibuprofen and thus these are called pain relievers.

Question 11

An oncogene

Answer 11

a mutated cellular gene whose activity can cause uncontrolled growth. A proto-oncogene is the unmutated cellular equivalent.

Question 12

Mutations of genes in signaling systems

Answer 12

can lead to tumor formation. These mutations primarily affect a structure/function or the level of expression of one of these genes.

Question 13

Mutation that results in change of the amino acid at position 11/12 or 61 of RAS

Answer 13

impedes its GTPase activity and result in RAS being left in the ON state. This creates an onogene that can stimulate a cell to continuously divide.

Question 14

Mutated RAS

Answer 14

the most common point mutation in cancer - found in 90% of pancreatic cancers and 20% of all cancers.

Question 15

src is a proto-oncogene that participates in controlling a cell’s decision to divide.

Answer 15

It too is a tyrosine kinase, but it is not a receptor tyrosine kinase. When its carboxy tail is phosphorylated on tyrosines, the cell does not divide. When the tail is not phosphorylated, it stimulates cell division. A viral form of src (derived from the cellular gene) is known that has been mutated such that it does not have the carboxy tail. It favors cancer by virtue of the fact that it can’t be turned off.