Question

Please answer all parts, thank you.

A.) What are the general terms for the MAPK signaling cascade enzymes? What are the specific names?

B.) Explain the BRAF V600E mutation and how it impacts MAPK signaling. What extracellular signal is required for MAPK activation when this mutation is present? Would an EGFR inhibitor be effective in BRAF V600E mutate cancer?

C.) PIP2 returns: what enzyme phosphorylates PIP2? What molecule is created? How is this different than PIP2 use in GPCR signaling?

D.) How does phosphorylation of PIP2 (from last question) activate AKT? (hint: it involves PDK1)

E.) What are two downstream signals of AKT that promote the overall growth and survival of cells?

F.) How does Grb2 play a role in the activation of both MAPK and Pi3K signaling? Does Grb2 have enzymatic activity?

G.) What is cyclinD1? Which signaling pathway converge on this target?

H.) How would kinase domain inactivation in RTKs inhibit signal cascades?

Answer 1

A)i)RAS-GRB2 and SOS stimulate RAS ,it is g protein and it has GTPase activity.

ii)RAF-RAS stimulates RAF .

iii)RAF- it phosphorylates MEK

iv)MEK-this kinase phosphorylates ERK(MAPK).

v)ERK/MAPK-activated MAPK phosphorylates ELK.

ELK-also called MAP,activated ELK binds with the DNA and activates transcription of jun and fos gene.

• RAS-Proto-oncogene protein p21-it is a membrane localized GTPase .
• RAF-RAS ASSOCIATED FACTOR ,it is ser,threonine kinase.
• MEK-MITOGENIC ACTIVATED PROTEIN KINASE .It has dual specificty.It can phosphorylates both ser/Thr and Tyrosine.
• ERK/MAPK-EXTRA CELLULAR SIGNAL REGULATED KINASE/MICROTUBULE ASSOCIATED PROTEIN KINASE.It is a Tyrosine kinase.