Physiology 534 Exam Iv: Receptor As A Tyrosine Pathway

Front 1

What happens when the ligand binds to the extracellular domain?

Back 1

Becomes activated and autophosphorylation via Tyrosine Kinase and ATP.

Front 2

Phosphorylated Tyrosine on the TK serves what purpose?

Back 2

Flag for SH2 domains

Front 3

SH2 domains (Src homology2)

Back 3

-Similar to Src oncogene
-recognize phosphorylation
-serve as a coupler/adapter btw TK & downstream signaling system.

Front 4

What are the 2 major signaling pathways?

Back 4

-MAP kinase
-Phosphatidyl-Inositol 3-OH Kinase

Front 5

MAP Kinase

Back 5

Uses exchange GTP-GDP factors & GTPases.

Front 6

Phosphatidyl Inositol 3-OH Kinase

Back 6

Uses lipids as signaling intermediates

Front 7

What is the coupler/adaptor for MAP Kinase?

Back 7

Grb2, contains SH2 domain proteins that recognize PO4-Tyr

Front 8

What is the exchange factor for MAP Kinase?

Back 8

Ras, gets phosphorylated to become RAS-GTP

Front 9

The 3 Ser/Thr Kinase cascade produce?

Back 9

1. ERK
2. p38 MAPK
3. JNK

Front 10

Once ERK comes into the nucleus it activates?

Back 10

c-fos-->activates genes-->cell division or proliferation-->cell growing/dividing

Front 11

Once p38 MAPK and JNK enter the nucleus it activates?

Back 11

c-jun-->transcription factors-->cell differentiation, inflammation, apoptosis

Front 12

What is the PI3 Kinase coupler/adaptor?

Back 12

PI3 Kinase, contains SH2 domain proteins that recognizes PO4-Tyr

Front 13

What is the lipid intermediate for the PI3 Kinase pathway?

What is the lipid signaling intermediate?

Back 13

PIP2 (4,5)

PIP3 (3, 4, 5)

Front 14

What is the coupler/adaptor for the insulin signaling system?

Back 14

IRS-1, contains SH2 domain that recognizes PO4-Tyr flag

Then can go to MAP Kinase or PI3 Kinase Pathway

Front 15

Type II diabetes can be caused by?

Back 15

1. Low # of insulin receptors
2. Defective insulin receptors (low/no TK activity)
3. Deficient/defective coupling of IRS-1

Front 16

When the receptor is NOT a Tyrosine Kinase (Ser/Thr Kinase instead), but non-covalently associated with TK

Back 16

Erythropotietin (ligand) binds, Recruit STAT, has SH2 which recognizes PO4-Tyr-->phosphorylated by JAK-->activates transcription in nucleus

Front 17

Receptor for transforming growth factor B

Back 17

Ligand binds-->recruits SARA-->phosphorylates SMAD-->goes into nucleus-->activates transcription

Rem: receptor IS an enzyme, not coupled to an enzyme

Front 18

Oncogene

Back 18

Gene for tumor-causing viruses responsible for transformation from a normal cell to a tumor cell

Front 19

Proto-oncogene

Back 19

Genes in normal cells that are similar/identical to viral oncogenes

c-onc, c-src, c-jun, c-fos

Front 20

Certain oncogenes are structurally similar to growth factors

Back 20

1. PDGF: platelet derived growth factor
similar to p28 (v-sis)

2. EGFR
Structurally similar to gp65 (v-erbB2)

Front 21

EGFR vs. V-erbB2

Back 21

V-erbB2 has no ligand-binding domain so no regulation of oncogene

-TK activity is always turned on (constitutively active), so no growth factors needed
-growth advantage to tumor cells

Front 22

What are the changes that normal cells need to undergo to become tumor cells?

Back 22

1. Self-sufficiency in growth signals
2. Insensitivity to anti-growth signals
3. Acquire angiogenesis property: growing of blood vessels to supply the tumor
4. metastasis