ch 23: Enzyme coupled receptors

growth factors mostly bind to

receptor tyrosine kinase ( RTKs)

when a ligand binds to an RTK it leads to the dimerization on

tyrosines

phosphorylated tyrosine residues privide bidning site for proteins with

SH2 domains

how is phospholipase C-gamma activated

it binds to phototyrosine residues using their SH2 domains

what does PLC-gama produce and how

it produces IP3 and DAG by cleaving PIP2

only activation of RTKs by growth factor is mitogenic and can also activate

Mitogen Activated Protein Kinase (MAP kinase)

describe how RTKs activate MAP kinase

1. Grb2 binds phosphotyrosine residues using SH2 domain

2. GRV2 uses its SH3 domain to binds to proline rich regions on Sos

3. Sos is a GEF for the G-protein Ras

4. Ras-GTP activates the protein kinase Rad

5. Raf phosphorylates MEK to activate it

6. MEK phosphorylates MAP kinase to activate it

7. MAP kinase phosphorylates transcription factor which activate the immediate early response genes

what are immediate early-response genes

transcribed first and transiently on response to growth factor simulation

what are some transcription factors

c-fos, c-jun, c-myc

after the immediate early response genes are transcribed the ___ is made

protein

what are the two sexes of yeast?

alpha and beta

describe yeast mating

haploid cells of the opposite sex fuse to become diploid

how is mating of yeast done

mating pheromones are released by one cell type and binds receptors on the opposite cell type leading to mating

how do yeast use MAP pathway to mate

1. mating pheromone binds to G-protein coupled receptor.

2. the beta gamma subunit recruits a scaffolding complex which contains several kinases.

3. phosphorylation cascade leads to activation of MAP kinase which phosphorylates proteins that lead to changes in gene expression required for mating

insuline secretes in response to

elevated blood glucose

insuline causes cell to take up glucose which causes

increase storage of glucose and increase metabolism glucose

the insuline receptor is a

tyrosine kinase

in insulin signaling the tyrosine kinase recruits and phosphorylates

Insuline Receptor Substrate 1 (IRS 1)

what happens after IRS 1 is phosphorylated

GRG2 binds phosh\photyrosine residues on IRS 1 leading to activation of the MAP kinase

T or F Insulin is a growth hormone

F. it is not

T or F insuline has complete effect to the amount of glucose that is uptaken

F. it has none

IRS-1 is alos bound to PI 3-kinase via

SH2 domain

PI 3-kinase phosphorylates phosphatidylinositol 4,5 bisphosphate on it’s #3 carbon to produce

PIP3

what does PIP3 provide?

binding sites for proteins with a plekstrin homology domain

two enzymes that have plekstrin homology domain are

phosphinositide dependent kinase (PDK) and akt (protein kinase B)

PDK and its substrate Akt binds near each other at the plasma membrane and once PDK phosphorylates

Akt is activated

Akt phosphorylates multiple proteins leading to the translocation of vesicles containing glucose transport proteins to the plasma membrane leading to

glucose uptake

Akt also phosphorylates proteins leading to increased ___ synthesis

glycogen

when is glycogen synthase active

when it’s dephosphorylated

PKA can inhibit glycogen synthase only when

PKA activity is really high

describe how Akt inhibits inhibition of glycogen synthase

Akt phosphorylates glucogen synthase kinase. Glycogen synthase kinase will inhibit glycogen synthase causing the phosphorylation of glycogen synthase making it inactive

how is focal adhesion able to be a binding site for so many pathways?

integrin binds to ecm and recruitsfocal adhesion kinase will be binding site for Src which is a soluble tyrosine kinase that phosphorylates additional tyrosine on FAK. Since PI 3-kinase, PLC-gamma and Grb2 use tyrosine to bind to them they can all bind in one site

growth and survival of cell is due to FAK and Src family being overreactive and over expressed leading to

cancer

focal adhesion signal and FAK signal lead to development and migration which regulates ___, ____, ____ to modify actin polymerization and organization

rho,rac,cdc42

what are serine/threonine kinases

transforming growth factor

what is the purpose of serine/threonine kinases

inhibits growth of most cells types and promotes tissue maturation by promoting synthesis of ECM component s

how is serine/threonine kinase activated

1. transforming growth factor beta binds recepto somposed of 2 type I and 2 type II

2. type II are going to bind to type II and they are activated

3. type II is going to phosphorylate type I receptors to activate them

4. activated receptor is a serine/threonine kinase which phosphorylates Smad transcription factor and inhibit growth