From Membrane to Nucleus: Teaching Cell Signaling
via the Ras Pathway
CELL BIOLOGY TEAM
Kathleen Marrs, IUPUIJames Marrs, IUPUIMariah Judd, IUPUITodd Murphy, Ivy Tech Community College (IUPUI)Robert Steven, University of ToledoTomer Avidor-Reiss, University of ToledoHenry Chang, Purdue University
Facilitators:Brian Kinkle, University of Cincinnati Sadie Hebert, University of Minnesota
CONTEXT
0This unit was prepared for a sophomore level cell biology course, taught mid way through the semester0 This unit was designed with the flexibility to be scaled
down to a freshman level biology course.0Unit designed to take 1-2 (one hour) class sessions
EXPECTED BACKGROUND
0Basics of cell structure and organelles 0Protein control by phosphorylation 0Understand that cells have the ability to respond to
extracellular stimuli0Basics 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) Analyze the effect of mutations on the components of the Ras pathway (BT 5-6)
b) 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) Create a schematic depicting the RTK/RAS/MAP kinase signaling pathway in both the active and inactive states. (BT 1-2)
b) 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) Analyze the effect of perturbation(s) on the components of the Ras pathway. (BT 4-5)
b) Develop the skill of analyzing data, controls and outcomes of experiments. (BT 4-5)
(BT=Bloom’s Taxonomy)
PRE-ASSIGNMENTS
0Read the introduction from “The History of Ras: the Saga Continues” by Cox and Der, 2010
0Review chapter section in text book that covers Ras pathway and review section questions
0MAPK pathway video by Genentech (Youtube video) with video reflections
PRE-ASSIGNMENTS
0Read the introduction from “The History of Ras: the Saga Continues” by Cox and Der, 2010
0Review chapter section in text book that covers Ras pathway and review section questions
0MAPK pathway video by Genentech (Youtube video) with video reflections
PRE-ASSIGNMENTS SUMMARY
Modulation of signalling by Sprouty: a developing storyHong Joo Kim & Dafna Bar-SagiNature Reviews Molecular Cell Biology 5, 441-450 (June 2004) doi:10.1038/nrm1400
From Membrane to Nucleus:
Teaching Cell Signaling via the Ras Pathway
Our Tidbit
Activation of a G-protein involves ___________.
a) Cleavage of the G-proteinb) Methylation of the G-proteinc) Binding of GTPd) Binding of GDPe) Techno music
Clicker Question
Ras is a __________.
a) Signal transduction moleculeb) Transcription factorc) Calcium channeld) Membrane receptore) Flavor of the Month at Starbucks
Clicker Question
WHY DO WE CARE ABOUT RAS?
0Ras is the most common oncogene in human cancer.0 90% of all pancreatic cancers0 25% of all human tumors
0The Ras pathway provides a focus on the origins of cancer at the molecular level.
0Ras is a key cellular protein for cell growth, differentiation and survival.
http://www.sciencephoto.com/
RAS-ZLE DAZZLE PUZZLE
Materials needed:0 One 8.5x11 puzzle board0 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 pathway modeling activity
RAS-ZLE DAZZLE PUZZLE
“OFF” State
RAS-ZLE DAZZLE PUZZLE
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 pathway modeling activity
RAS-ZLE DAZZLE PUZZLE
“ON” State
What initially triggers a change in gene expression (in a WT cell)?
a) Ras Activationb) GTP Hydrolysisc) MAP Kinase Phosphorylationd) Growth Factor – Receptor binding
Clicker Question
RAS-ZLE DAZZLE PUZZLE:WHAT IS THE SIGNIFICANCE?
0What is the significance and outcome of…
0 the receptor – ligand interaction0 the Ras activation0 the MAP kinase cascade
0What is the significance of the ERK translocation and what is one possible outcome?
WHEN GOOD CELLS GO BAD:DISRUPTIONS IN THE PATHWAY
0What happens when we perturb the pathway?
Summative Assessment
SUMMATIVE HOMEWORK
0Practice with data analysis, controls and outcomes.
0Uses 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
0Nobel laureate0Discovered growth
factor signaling0 Italian Jewish
scientist0Lived to age 103
Image
TIDBITGOALS AND OUTCOMES
Know specific components and relationship between components of the Ras pathway affecting cell
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)
Goal I
Outcome a)
Outcome b)
With thanks to HHMI, The University of Minnesotaand the National Academies NorthStar (Midwest) Summer Institute (NANSI):
Thanks also to
Brian and Sadie,
our amazing
facilitators