A pharmaceutical company developed a drug, CP788, that inhibits the interaction of Grb2 with SH2 domains as a treatment for breast cancer. As the data below shows, the compound inhibits activation of RAS in MDA-MB-468 breast cancer cells (Figure A) and anchorage-dependent growth (Figure B solid line) in MDA-MB-468 breast cancer cells. Note that these experimets were done in the presence of EGF. Briefly explain the steps in the pathway by which inhibition of Grb2/SH2 interaction would inhibit activation of RAS (limit 5-6 sentences). A % RAS Activation Inhibition of RAS Activation by CP788 120 100 80 60 40 20 0 0 50 [CP788] UM 100 B Colonies number (% of untreated control) 120 100 80 60 40 20 0 10-2 10.¹ 10⁰ 10¹ 10² [CP788] UM 10³
A pharmaceutical company developed a drug, CP788, that inhibits the interaction of Grb2 with SH2 domains as a treatment for breast cancer. As the data below shows, the compound inhibits activation of RAS in MDA-MB-468 breast cancer cells (Figure A) and anchorage-dependent growth (Figure B solid line) in MDA-MB-468 breast cancer cells. Note that these experimets were done in the presence of EGF. Briefly explain the steps in the pathway by which inhibition of Grb2/SH2 interaction would inhibit activation of RAS (limit 5-6 sentences). A % RAS Activation Inhibition of RAS Activation by CP788 120 100 80 60 40 20 0 0 50 [CP788] UM 100 B Colonies number (% of untreated control) 120 100 80 60 40 20 0 10-2 10.¹ 10⁰ 10¹ 10² [CP788] UM 10³
Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
Section: Chapter Questions
Problem 1P
Related questions
Question
![A pharmaceutical company developed a drug, CP788, that inhibits the interaction of Grb2 with SH2 domains as a treatment for breast cancer. As the
data below shows, the compound inhibits activation of RAS in MDA-MB-468 breast cancer cells (Figure A) and anchorage-dependent growth (Figure B
solid line) in MDA-MB-468 breast cancer cells. Note that these experimets were done in the presence of EGF. Briefly explain the steps in the pathway
by which inhibition of Grb2/SH2 interaction would inhibit activation of RAS (limit 5-6 sentences).
A Inhibition of RAS Activation by CP788
% RAS Activation
120
100
80
60
20
0
0
50
[CP788] UM
100
B
Colonies number (% of
untreated control)
120
100
80
60
40
20
0
10-²
HigHt
10-¹
10⁰ 10¹ 10² 10³
[CP788] UM](/v2/_next/image?url=https%3A%2F%2Fcontent.bartleby.com%2Fqna-images%2Fquestion%2F1896aee9-4e1b-4aca-9af3-0b7f8caac28e%2Fa1b489c0-931d-4925-b517-f0d2f0ef1493%2F8qifz1ar_processed.png&w=3840&q=75)
Transcribed Image Text:A pharmaceutical company developed a drug, CP788, that inhibits the interaction of Grb2 with SH2 domains as a treatment for breast cancer. As the
data below shows, the compound inhibits activation of RAS in MDA-MB-468 breast cancer cells (Figure A) and anchorage-dependent growth (Figure B
solid line) in MDA-MB-468 breast cancer cells. Note that these experimets were done in the presence of EGF. Briefly explain the steps in the pathway
by which inhibition of Grb2/SH2 interaction would inhibit activation of RAS (limit 5-6 sentences).
A Inhibition of RAS Activation by CP788
% RAS Activation
120
100
80
60
20
0
0
50
[CP788] UM
100
B
Colonies number (% of
untreated control)
120
100
80
60
40
20
0
10-²
HigHt
10-¹
10⁰ 10¹ 10² 10³
[CP788] UM
Expert Solution
Biochemical signaling involving Grb2 with SH2 domains and Ras
Grb2 ( growth factor receptor bound protein 2) is an adaptor protein whose function is to bring together 2 different proteins to enable signal transduction. SH2 and SH3 are 2 protein binding domains in Grb2. SH2 domain binds to a phosphorylated tyrosine residue on a protein while SH3 domain binds to a second protein's proline rich region.
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