From Membrane to Nucleus:
Teaching Cell Signaling
via the Ras Pathway
CELL BIOLOGY TEAM
Kathleen Marrs, IUPUI
James Marrs, IUPUI
Mariah Judd, IUPUI
Todd Murphy, Ivy Tech Community College (IUPUI)
Robert Steven, University of Toledo
Tomer Avidor-Reiss, University of Toledo
Henry Chang, Purdue University
Facilitators:
Brian Kinkle, University of Cincinnati
Sadie Hebert, University of Minnesota
CONTEXT
0 This unit was prepared for a sophomore level cell
biology course, taught mid way through the semester
0 This unit was designed with the flexibility to be scaled
down to a freshman level biology course.
0 Unit designed to take 1-2 (one hour) class sessions
EXPECTED BACKGROUND
0 Basics of cell structure and organelles
0 Protein control by phosphorylation
0 Understand that cells have the ability to respond to
extracellular stimuli
0 Basics of cell signaling cascades (including various
types of G-proteins)
TEACHABLE UNIT
GOALS AND OUTCOMES
I.
Know specific components and relationship between
components of the Ras pathway affecting cell proliferation.
a)
Order the sequence of proteins involved in the Ras pathway and
describe their cellular location (BT 1-2)
b)
Describe the role of each component of the Ras pathway (BT 2-3)
II. Evaluate the consequences of perturbations to the signaling
pathway using real data.
a)
b)
Analyze the effect of mutations on the components of the Ras
pathway (BT 5-6)
Practice the skill of analyzing data, controls and outcomes of
experiments. (BT 4-5)
TEACHABLE UNIT
GOALS AND OUTCOMES
I.
Know specific components and relationship between
components of the Ras pathway affecting cell proliferation.
a)
b)
Create a schematic depicting the RTK/RAS/MAP kinase signaling
pathway in both the active and inactive states. (BT 1-2)
Discuss the role and significance of each component of the Ras
pathway. (BT 2-3)
II. Evaluate the consequences of perturbations to the signaling
pathway using real data.
a)
b)
Analyze the effect of perturbation(s) on the components of the Ras
pathway. (BT 4-5)
Develop the skill of analyzing data, controls and outcomes of
experiments. (BT 4-5)
(BT=Bloom’s Taxonomy)
PRE-ASSIGNMENTS
0 Read the introduction from “The History of Ras: the
Saga Continues” by Cox and Der, 2010
0 Review chapter section in text book that covers Ras
pathway and review section questions
0 MAPK pathway video by Genentech (Youtube video)
with video reflections
PRE-ASSIGNMENTS
0 Read the introduction from “The History of Ras: the
Saga Continues” by Cox and Der, 2010
0 Review chapter section in text book that covers Ras
pathway and review section questions
0 MAPK pathway video by Genentech (Youtube video)
with video reflections
PRE-ASSIGNMENTS SUMMARY
Modulation of signalling by Sprouty: a developing story
Hong Joo Kim & Dafna Bar-Sagi
Nature Reviews Molecular Cell Biology
5, 441-450 (June 2004) doi:10.1038/nrm1400
Activation of a G-protein
involves ___________.
a) Cleavage of the G-protein
b) Methylation of the G-protein
c) Binding of GTP
d) Binding of GDP
e) Techno music
Ras is a __________.
a) Signal transduction molecule
b) Transcription factor
c) Calcium channel
d) Membrane receptor
e) Flavor of the Month at Starbucks
WHY DO WE CARE ABOUT RAS?
0 Ras is the most common oncogene in human cancer.
0 90% of all pancreatic cancers
0 25% of all human tumors
0 The Ras pathway
provides a focus on the
origins of cancer at the
molecular level.
0 Ras is a key cellular
protein for cell growth,
differentiation and
survival.
http://www.sciencephoto.com/
RAS-ZLE DAZZLE PUZZLE
Ras pathway modeling activity
Materials needed:
0 One 8.5x11 puzzle board
0 2 Envelopes labeled #1 “OFF” and #2 “ON” filled with puzzle
pieces
Working with your pod…
0 First: read and open envelope #1 “OFF” and assemble the pieces
in the appropriate place on the puzzle board. (5 minutes)
0 Second: share your puzzle with the other pods at your table to
compare and discuss. (5 minutes)
RAS-ZLE DAZZLE PUZZLE
“OFF” State
RAS-ZLE DAZZLE PUZZLE
Ras pathway modeling activity
Working with your pod…
0 Third: read and open envelope #2 “ON” and add the new pieces
to the puzzle board. (5 minutes)
0 Fourth: share your completed puzzle with the other pods at your
table to compare and discuss. (5 minutes)
RAS-ZLE DAZZLE PUZZLE
“ON” State
What initially triggers a change in
gene expression (in a WT cell)?
a) Ras Activation
b) GTP Hydrolysis
c) MAP Kinase Phosphorylation
d) Growth Factor – Receptor binding
RAS-ZLE DAZZLE PUZZLE:
WHAT IS THE SIGNIFICANCE?
0 What is the significance and outcome of…
0 the receptor – ligand interaction
0 the Ras activation
0 the MAP kinase cascade
0 What is the significance of the ERK translocation
and what is one possible outcome?
WHEN GOOD CELLS GO BAD:
DISRUPTIONS IN THE PATHWAY
0 What happens when we perturb the pathway?
Summative
Assessment
SUMMATIVE HOMEWORK
0 Practice with data
analysis, controls
and outcomes.
0 Uses real data from
primary literature.
Summative
Assessment
RITA LEVI-MONTALCINI
“Above all, don’t fear difficult moments.
The best comes from them.”
In Praise of Imperfection, Levi-Montalcini’s biography
0 Nobel laureate
0 Discovered growth
factor signaling
0 Italian Jewish
scientist
0 Lived to age 103
Image
TIDBIT
GOALS AND OUTCOMES
Goal I Know specific components and
relationship between components of the
Ras pathway affecting cell
Outcome a) Create a schematic depicting the RTK/RAS/MAP
kinase signaling pathway in both the active and
inactive states.(BT 1-2)
Outcome b) Discuss the role and significance of each component
of the Ras pathway(BT 2-3)