Chapt. 14 Signal Transduction (also called Cell Signaling) : Chapt. 14 Signal Transduction (also called Cell Signaling) Fun! Fun! Fun! Like a vacation!
Easy and Entertaining! No Headaches! No math!
WE COVERED ELECTRICAL SIGNALING (or membrane potential) CONTROLLING CELLS IN CHAPT. 9, NOW WE TALK ABOUT
HOW HORMONES WORK!!
CHEMICAL MESSENGERS AND THEIR RECEPTORS-
INSULIN ACTS THROUGH BINDING ITS RECEPTOR
2 TYPES OF CHEMICAL MEDIATORS: : 2 TYPES OF CHEMICAL MEDIATORS: ENDOCRINE PARACRINE
ANIMATION : ANIMATION D:\cell biol 3611\apop cell signaling\ENDOCR LOCAL MEDIATOR A0010401.MOV
SIGNAL TRANSDUCTION OVERVIEW : SIGNAL TRANSDUCTION OVERVIEW 1. CHEMICAL MEDIATORS (CH .14)
A. HORMONES – ENDOCRINE- GO THROUGH BLOOD STREAM
B. LOCAL MEDIATORS- RELEASED BY ONE CELL, DIFFUSES (CH. 8-9) TO NEXT FEW CELLS LOCATED NEARBY. HISTAMINE, GROWTH FACTORS IN SOME CANCERS
2. CELL TO CELL CONTACT (CH 17)
3. ELECTRICAL (CH. 13)
NOBEL LAUREATES (MEDICINE 1985-2003) ALMOST ALL IN SIGNAL TRANSDUCTION : NOBEL LAUREATES (MEDICINE 1985-2003) ALMOST ALL IN SIGNAL TRANSDUCTION 2003 Paul C. Lauterbur, Sir Peter Mansfield 2002 Sydney Brenner, H. Robert Horvitz, John E. Sulston 2001 Leland H. Hartwell, Tim Hunt, Sir Paul Nurse 2000 Arvid Carlsson, Paul Greengard, Eric R. Kandel 1999 Günter Blobel 1998 Robert F. Furchgott, Louis J. Ignarro, Ferid Murad 1997 Stanley B. Prusiner 1996 Peter C. Doherty, Rolf M. Zinkernagel 1995 Edward B. Lewis, Christiane Nüsslein-Volhard, Eric F. Wieschaus 1994 Alfred G. Gilman, Martin Rodbell 1993 Richard J. Roberts, Phillip A. Sharp 1992 Edmond H. Fischer, Edwin G. Krebs 1991 Erwin Neher, Bert Sakmann 1990 Joseph E. Murray, E. Donnall Thomas 1989 J. Michael Bishop, Harold E. Varmus 1988 Sir James W. Black, Gertrude B. Elion, George H. Hitchings 1987 Susumu Tonegawa 1986 Stanley Cohen, Rita Levi-Montalcini 1985 Michael S. Brown, Joseph L. Goldstein
Slide6 : INTEGRAL MEMBRANE
PROTEIN HORMONE,
CHEMICAL MEDIATOR IMPT KEY HERE TURN ON OR OFF CERTAIN GENES WHAT BONDS
BETWEEN LIGAND
AND RECEPTOR?
FALL 2006 EXAM 1 AVER: 66. FIND EXAM- NAMES ENDING IN your left:A-K MIDDLE: L-S your rt: T-Z : FALL 2006 EXAM 1 AVER: 66. FIND EXAM- NAMES ENDING IN your left:A-K MIDDLE: L-S your rt: T-Z You can drop an exam; remember to add in extra credit homework
SAMPLE GRADE CALCULATION:
SCANTRON PORTION: 65 POSSIBLE POINTS, 29 QUESTIONS WORTH 2.24 POINTS EACH
NUMBER CORRECT ON SCANTRON TO RIGHT; IF SCORE IS 20, THEN 20 X 2.24 = 44.8, ROUND UP TO 45 PTS.
THEN ADD IN THE POINTS IN THE WRITTEN SECTION
TOTAL POSSIBLE: 100 PTS
General plan for Signal Transduction : General plan for Signal Transduction Transduction: to carry the signal across the plasma membrane
Hormone binds receptor, cascade of events often leads to turning on a transcription factor
Transcription factors bind DNA to turn on (or off) certain genes
New proteins made to change the cell
D:\cell biol 3611\apop cell signaling\cellsig-general.mov
RECEPTORS : RECEPTORS INTEGRAL MEMBRANE PROTEINS
TO THRU MEMBRANE WITH ALPHA HELIX
HUGE -AVERAGE PROTEIN IN DALTONS:
VS. RECEPTOR AT 400,000 DALTONS
VERY HIGH AFFINITY FOR HORMONE- WHY?
HORMONE BINDS THRU WEAK BONDS, DISTORTS RECEPTOR TO TURN IT ON
RECEPTOR CAUSES SECOND MESSENGERS TO BE MADE AND RELEASED INTO CYTOPLASM
RECEPTOR DOWNREGUATION : RECEPTOR DOWNREGUATION RECEPTOR STILL BOUND BY HORMONE, BUT RECEPTOR TURNS OFF BECAUSE
REMOVE RECEPTOR FROM PLASMA MEMBRANE BY RECEPTOR-MEDIATED ENDOCYTOSIS (CH. 12)
A KINASE (CH. 6) PUTS A PHOSPHATE (OR PHOSPHORYL) FUNC GRP ON RECEPTOR TO TURN OFF RECEPTOR
SOME 70% OF MEDICINES WORK ON RECEPTORS: : SOME 70% OF MEDICINES WORK ON RECEPTORS: TOLERANCE: NEOSYNEPHRINE NASAL SPRAY STOPS WORKING AFTER A WHILE DUE TO RECEPTOR DOWN REGULATION
ISOPROTERENOL STIMULATES BETA EPINEPHRINE RECEPTOR (STIMULATING HEART)
PROPRANOLOL INHIBITS BETA EPINEPHRINE RECEPTOR (REDUCES HEART BEAT)
3 FAMILES OF RECEPTORS IN THE PLASMA MEMBRANE : 3 FAMILES OF RECEPTORS IN THE PLASMA MEMBRANE 1. Ligand gated Channel (see ch. 13) RECEPTOR LINKED TO ION CHANNEL
E.G., ACETYLCHOLINE RECEPTOR (SEE OUR WEB SITE ANIMATION; CH. 8/9) THIS CAN BE A VOLTAGE gated ION CHANNEL OR A LIGAND GATED ION CHANNEL. Use the Nerst equation to calc the Vm before and after Ach added.
2. G PROTEIN LINKED RECEPTOR
3. RECEPTOR LINKED TO KINASE
2. G PROTEIN LINKED RECEPTOR : 2. G PROTEIN LINKED RECEPTOR D:\cell biol 3611\apop cell signaling\cellsig-gprotein.mov
HORMONE BINDS RECEPTOR, RECEPTOR TURNS ON G PROTEIN, G PROTEIN TURNS ON OTHER PROTEINS
G PROTEINS BIND GTP
Very large no of Receptors that turn on G proteins –they span the membrane 7 times : Very large no of Receptors that turn on G proteins –they span the membrane 7 times Figure from “The magnificent seven” science article
Slide15 : FIG. 14-5
ANIMATION OF G PROTEIN ACTIVATION : ANIMATION OF G PROTEIN ACTIVATION 2 on our course web site:
http://dkc.mse.jhu.edu/~teal/gprotein.html
Another G protein animation:
D:\cell biol 3611\apop cell signaling\G PROT ARRESTIN MBC 15_5.mov (sound)
Slide17 : GTP ATP P – P – P - P – P – P - SUGAR SUGAR N BASE
A N BASE
G ENERGY SOURCE AND REGULATOR FOR MICROFILAMENTS
(IF ONE PHOSPHATE, MAKES UP DNA ALSO)
REGULATOR
(IF ONE PHOSPHATE,
MAKES UP DNA ALSO) cAMP SUGAR N BASE
A P C = CYCLIC;
A Second
Messenger;
REGULATOR
Slide18 : FIG. 14-7
FIRST SYSTEM
cAMP system
(note it uses a G protein)
Slide19 : This G protein is called
Gs because it stimualtes adenylyl cyclase
(Gi inhibits) STIMULATES
PROTEIN KINASE A
PROTEIN KINASE A ACTIVATED BY 2 cAMP molecules fig. 14-8 : PROTEIN KINASE A ACTIVATED BY 2 cAMP molecules fig. 14-8
G protein activates Adenylyl Cyclase, Protein kinase A, and then a transcription factor : G protein activates Adenylyl Cyclase, Protein kinase A, and then a transcription factor D:\cell biol 3611\apop cell signaling\MBC cAMP 15_4.mov
From our text (a bit too simple) D:\cell biol 3611\apop cell signaling\camp.mov D:\cell biol 3611\apop cell signaling\epi cAMP.mov : From our text (a bit too simple) D:\cell biol 3611\apop cell signaling\camp.mov D:\cell biol 3611\apop cell signaling\epi cAMP.mov HOW EPINEPHRINE WORKS
Summary of how cAMP signal is turned off : Summary of how cAMP signal is turned off HORMONE LEVELS DECLINE
ALPHA SUBUNIT OF G PROTEIN TURNS ITSELF OFF (BREAKS DOWN GTP TO GDP)
BETA AND GAMMA SUBUNITS AGAIN BIND TO ALPHA SUBUNIT TO INHIBIT ALPHA
cAMP IS BROKEN DOWN BY PHOSPHODIESTERASE
THIS PHOSPHODIESTERASE IS TARGET OF MANY MEDICINES THAT RAISE cAMP (e.g, some diuretics)
Two G protein Diseases : Two G protein Diseases 1. CHOLERA BACTERIUM RELEASES A TOXIN THAT ENTERS THE CELL
AND PREVENTS Gs FROM BREAKING DOWN GTP TO GDP; THUS GS ALWAYS ON
THIS MEANS THAT ADENYLYL CYCLASE IS ALWAYS STIMULATED...SO
TOO MUCH cAMP IS MADE
DIARRHEA DEATH THRU DEHYDRATION
2. PERTUSSIS TOXIN; INHIBITS Gi
SO CAN’T SHUT OFF ADENYLYL CYCLASE
CAUSES WHOOPING COUGH
SECOND SYSTEM: InsP3 (OR IP3) SYSTEM (I simplified fig. 14-9) : SECOND SYSTEM: InsP3 (OR IP3) SYSTEM (I simplified fig. 14-9) IP3 released by ACETYLCHOLINE
PIP2: 2 fatty acids, Glycerol backbone, Phosphate and
Charged molecule (inositol with P) P FACE OF
MEMBRANE P inositol
SUGAR P P PHOSPHOLIPASE C THIS FRAGMENT IS
IP3 WHICH THEN
CAUSES RELEASE
OF CALCIUM INSIDE CELL THIS PHOSPHOLIPID IS PIP2 (sugar with 2 extra phosphates)
Slide26 : SECOND
SIGNAL
TRANSDUCTION
SYSTEM-
THE InsP3 OR
IP3 SYSTEM
THIS IS
PHOSPHOLIPASE
C BETA FORM
AND Gq
(NOT Gs OR Gi)
Slide27 : BOOK ERROR:
ACTIVE DAG IS WHAT
IS LEFT IN
MEMBRANE: (NOT cAMP-dept PROTEIN KINASE A)
ANIMATION OF IP3 SYSTEM : ANIMATION OF IP3 SYSTEM D:\cell biol 3611\apop cell signaling\PI turnover mcbio.mov
(IGNORE “SOC)
2 TYPES OF PHOSPHOLIPASE C: : 2 TYPES OF PHOSPHOLIPASE C: PLC BETA; ACTIVATED BY G PROTEINS CALLED Gq (THIRD TYPE OF G PROTEIN)
PLC GAMMA; ACTIVATED BY TYROSINE KINASE (A KINASE THAT PUTS PHOSPHATE ON TYROSINE
TYROSINE IS SAME AMINO ACID THAT WE DISCUSSED IN CARBOXYPEPTIDASE A MECHANISM
PHOSPHOLIPASE C –GAMMA ACTIVATION BY TYR KINASE: : PHOSPHOLIPASE C –GAMMA ACTIVATION BY TYR KINASE:
Summary: PLC gamma activation through tyrosine kinase and beta activation through G protein : Summary: PLC gamma activation through tyrosine kinase and beta activation through G protein
D:\cell biol 3611\apop cell signaling\rectyr.mov
D:\cell biol 3611\apop cell signaling\plc becker.mov
Second type of PLC, PHOSPHOLIPASE C GAMMA, ACTIVATED BY TYR. KINASE; DISCUSSED LATER IN TEXT : Second type of PLC, PHOSPHOLIPASE C GAMMA, ACTIVATED BY TYR. KINASE; DISCUSSED LATER IN TEXT WHAT DOES RELEASE OF CALCIUM INTO CYTOPLASM CAUSE?
CALCIUM BINDS AND ACTIVATES CALMODULIN
Slide33 : WHEN
Ca BINDS
THIS
BENDS 90o
WHY?
First example of IP3 system: CALCIUM RELEASE AT FERTILIZATION (PLC-GAMMA) (see FIG. 14-14) : First example of IP3 system: CALCIUM RELEASE AT FERTILIZATION (PLC-GAMMA) (see FIG. 14-14) Sperm bind and turn on a tyrosine kinase, stimulate PLC gamma, increasing IP3, and then calcium increases–
and a wave of elevated calcium travels across the egg
This begins fertilization
D:\cell biol 3611\apop cell signaling\ca wave fert.mov
2nd example of IP3; EPINEPHRINE STIM. BOTH cAMP and IP3 PATHS : 2nd example of IP3; EPINEPHRINE STIM. BOTH cAMP and IP3 PATHS FIG. 14-23 Gq, Gi or
Gs??
CALCIUM SIGNALING—SUMMARY AND BIG PICTURE BEFORE IP3 INCREASES, NOTE THAT CELLS KEEP CALCIUM VERY VERY LOW IN THE CYTOPLASM-- HOW? TWO MEMBRANE PROTEINS CALLED CALCIUM PUMPS REMOVE CALCIUM ALSO, NOTE THAT CALCIUM CAN INCREASE DUE TO OPENING OF CA CHANNEL IN PLASMA MEMBRANE : CALCIUM SIGNALING—SUMMARY AND BIG PICTURE BEFORE IP3 INCREASES, NOTE THAT CELLS KEEP CALCIUM VERY VERY LOW IN THE CYTOPLASM-- HOW? TWO MEMBRANE PROTEINS CALLED CALCIUM PUMPS REMOVE CALCIUM ALSO, NOTE THAT CALCIUM CAN INCREASE DUE TO OPENING OF CA CHANNEL IN PLASMA MEMBRANE
Slide37 : LIGAND OR VOLTAGE REG. CHANNEL 2 Ca
PUMPS PLC
BETA OR
GAMMA?
Summary FIRST 2 SYSTEMS: : Summary FIRST 2 SYSTEMS: 1st SYSTEM: cAMP PATH; HORMONE BINDS SERPENTINE RECEPTOR, TURNS ON G PROTEIN, TURNS ON ADENYLYL CYCLASE, cAMP LEVELS INCREASE, PKA STIMULATED
2ND SYSTEM: IP3 PATH, TWO TYPES:
SERPENTINE RECEPTOR TURNS ON G PROTEIN, PHOSPHOLIPASE C BETA, PIP2 BROKEN DOWN TO IP3 (CALCIUM RELEASE) AND DAG (PKC).
RECEPTOR IS A TYROSINE KINASE THAT TURNS ON PHOSPHOLIPASE C GAMMA.
3rd SYSTEM: NITRIC OXIDE (NO) CAUSES VASO- DILATION : 3rd SYSTEM: NITRIC OXIDE (NO) CAUSES VASO- DILATION SAME
IP3 SYSTEM
AS IN
FIG. 14-16 NEW
ENZYME GUANYLYL
CYLASE MAKES
cGMP (NOT cAMP) BOND?
NO SYSTEM; NOBEL IN 1999 : NO SYSTEM; NOBEL IN 1999 ACETYLCHOLINE EXPANDS BLOOD VESSELS
INCLUDING DURING PENILE ERECTION
VIGAGRA PREVENTS THE DESTRUCTION OF cGMP
VIAGRA INHIBITS cGMP PHOSPHODIESTERASE
4TH SYSTEM: TYROSINE KINASES : 4TH SYSTEM: TYROSINE KINASES WE ALREADY DISCUSSED; HORMONE BINDS RECEPTOR, RECEPTOR IS A TYROSINE KINASE
2 RECEPTORS HAVE TO DIMERIZE
THE DIMERIZED RECEPTORS TURN EACH OTHER ON- autophosphorylation
RECEPTORS TURN ON PHOSPHOLIPASE C GAMMA
EXAMPLES: INSULIN, GROWTH FACTORS
4TH SYSTEM: TYROSINE KINASES : 4TH SYSTEM: TYROSINE KINASES DIMERIZATION
AUTOPHOSPHORYLATION INSULIN
&
GROWTH
FACTORS
USE THIS
TYPE OF
RECEPTOR ON RECEPTORS ARE OFF
When HER2 (human epidermal growth factor receptor 2) gene is found in multiple copies, extra HER2 protein receptors are produced and this over-expression of HER2 causes 20% to 30% of breast cancer. Herceptin is an antibody that binds to EGF receptor 2 (HER2) and blocks the activation of EGF receptors : When HER2 (human epidermal growth factor receptor 2) gene is found in multiple copies, extra HER2 protein receptors are produced and this over-expression of HER2 causes 20% to 30% of breast cancer. Herceptin is an antibody that binds to EGF receptor 2 (HER2) and blocks the activation of EGF receptors
Help session for Exam 2 2006 : Help session for Exam 2 2006 North Classroom 1533
4-5 pm
Oct. 18 Wed (day before exam 2)
Today’s lecture material is the last for Exam 2
REMEMBER to use the free tutoring at the Center for Learning Assistance (2 bio tutors…)
NOW PROTEINS WITH AN “SH2” DOMAIN CAN BIND TO THE PHOSPHORYLATED TYROSINES : NOW PROTEINS WITH AN “SH2” DOMAIN CAN BIND TO THE PHOSPHORYLATED TYROSINES SEE ANIMATION PHOSPHOLIPASE C GAMMA SH2 DOMAIN OF
PLC GAMMA NOW PLC GAMMA
ON
4TH SYSTEM CONT’D: TYROSINE KINASE TURNS ON MAP KINASE PATH : 4TH SYSTEM CONT’D: TYROSINE KINASE TURNS ON MAP KINASE PATH DON’T MEMORIZE STEPS GRB2
HAS SH2 MAP KINASE TURNS
ON TRANSCRIPTION FACTORS,
TURNS ON GENES
RECEPTOR TYROSINE KINASE PATH LINKS TO (1) PLC AND (2)MAP KINASE PATH; SEE ANIMATIONS (note; click on for my my hard drive) : RECEPTOR TYROSINE KINASE PATH LINKS TO (1) PLC AND (2)MAP KINASE PATH; SEE ANIMATIONS (note; click on for my my hard drive) D:\cell biol 3611\apop cell signaling\rectyr.mov
D:\cell biol 3611\apop cell signaling\plc becker.mov
http://biocreations.com/pages/bioanimations.html then click on animation or…
D:\cell biol 3611\apop cell signaling\MAPK1.swf (Biocreations)
Review the animations on the class web site. See more info on the receptor tyrosine kinases and cancer/human disease.
4TH PATH CONT’D: (don’t memorize for exam) : 4TH PATH CONT’D: (don’t memorize for exam) ANTHRAX ACTS IN PART BY INACTIVATING MAP KINASE PATH (SCI 280:734, 1998)
This web site centers in on the epidermal growth factor (EGF) receptor and drugs that inhibit this receptor TYROSINE kinase will stop cancer. For example, AstraZeneca has a drug called Iressa, Novartis has Gleevec and Genentech has Herceptin. Old: http://www.egfr-info.com/
Erbitux (ImClone, Bristol-Myers Squibb Co) is another antibody to EGF receptor and this drug was associated with the stock scandal that caused Martha Stewart jail time! At first, they thought it did not work (stock went downhill); now they think it DOES! POOR MARTHA!
Slide49 : 52% decrease in the recurrence of breast cancer
THE GOOD (BCL-2), : THE GOOD (BCL-2), THE BAD APOPTOSIS: AND THE UGLY
5TH SYSTEM; APOPTOSIS : 5TH SYSTEM; APOPTOSIS NECROSIS (CELL APOPTOSIS
BURSTS; (NO BURSTING
INFLAMMATION). OR INFLAMMATION).
NORMAL CELL ENGULFS
THE APOPTOTIC CELL. (FROM MOL BIO CELL)
WHY IS APOPTOSIS IMPORTANT? : WHY IS APOPTOSIS IMPORTANT? NEEDED FOR DEVELOPMENT OF EMBRYO, SCULPTING OF ORGANS, BODY
NOBEL PRIZE ON APOPTOSIS: “MANY (CANCER) TREATMENT STRATEGIES ARE BASED ON STIMULATION OF THE CELLULAR 'SUICIDE PROGRAM.”
~ SO CANCER CELLS WOULD KILL THEMSELVES!
EXAMPLES OF APOPTOSIS OR PROGRAMMED CELL SUICIDE: : EXAMPLES OF APOPTOSIS OR PROGRAMMED CELL SUICIDE: If UV light damages a cell’s DNA, then that cell will undergo cell suicide (apoptosis)- if not cancer.
EMBRYONIC BRAIN HAS TOO MANY CELLS; MANY DIE BY APOPTOSIS (IF APOPTOSIS IS PREVENTED, RETARDATION RESULTS).
Slide54 : NORMAL MICE NO APOPTOSIS IF BLOCK APOPTOSIS==
OVERPROLIFERATION
OF BRAIN CELLS CAUSES
MENTAL PROBLEMS,
WEBBED DIGITS
OF MOUSE EMBRYO
EXAMPLES OF APOPTOSIS OR PROGRAMMED CELL SUICIDE: : EXAMPLES OF APOPTOSIS OR PROGRAMMED CELL SUICIDE: EMBRYOS HAVE WEBBING-
THE WEBBING CELLS ARE PROGRAMMED
TO UNDERGO APOPTOSIS!
Rat embryonic digits (Mol Bio Cell)
EXAMPLES OF APOPTOSIS OR PROGRAMMED CELL SUICIDE: : EXAMPLES OF APOPTOSIS OR PROGRAMMED CELL SUICIDE: LOSS OF TADPOLE TAIL
APOPTOSIS AND HUMAN HEALTH : APOPTOSIS AND HUMAN HEALTH EXCESSIVE APOPTOSIS OCCURS IN AIDS, NEUROGENERATIVE DISEASES, STROKE AND MYOCARDIAL INFARCTION.
IN OPPOSITION, IN AUTOIMMUNE DISEASE OR CANCER, THERE IS AN INHIBITION OF APOPTOSIS (LEADING TO THE SURVIVAL OF CANCER CELLS)
BCL-2 IS CENTRAL TO APOPTOSIS : BCL-2 IS CENTRAL TO APOPTOSIS ALL CELLS OF THE EMBRYO WOULD DIE EXCEPT THAT BCL-2 IS ACTIVATED IN SOME AND THESE CELLS SURVIVE.
SO, MUTATE BCL-2 (KILLING THE GENE), ALL EMBRYONIC CELLS DIE.
CAN WE MUTATE BCL-2 IN HUMAN CANCER CELLS, KILLING THE CANCER?
OR SAVE DESIRED, DYING CELLS BY TURNING ON BCL-2?
FIG. 14-25 APOPTOSIS PROCESS : FIG. 14-25 APOPTOSIS PROCESS
2 PATHS TO APOPTOSIS : 2 PATHS TO APOPTOSIS FAS INDUCES APOPTOSIS
TROPHIC FACTOR NOT PRESENT
Slide61 : Same path, different figure:
THE FAS PATH TO APOPTOSIS FROM MOLECULAR BIOL OF THE CELL STARTS
APOPTOSIS
CELL DEATH SIGNAL SIMPLIFY: FAS LIGAND BINDS TO FAS. FAS TURNS ON CASPASE 3 CASPASE 3 EXECUTES THE CELL : CELL DEATH SIGNAL SIMPLIFY: FAS LIGAND BINDS TO FAS. FAS TURNS ON CASPASE 3 CASPASE 3 EXECUTES THE CELL
Slide63 : BAD IS
TURNED
OFF BY THE
TROPHIC
FACTOR
RECEPTOR
BCL-2
PREVENTS
APOPTOSIS SECOND
PATH
TROPHIC
FACTOR
ABSENT
OR DNA
DAMAGED-
BAD IS
ON,
INHIBITS
BCL-2
2ND PATH TO APOPTOSIS AGAIN : 2ND PATH TO APOPTOSIS AGAIN NO TROPHIC FACTOR OUTSIDE CELL OR DNA DAMAGE BAD
IS ON BAD INHIBITS BCL-2 BCL-2 NO LONGER INHIBITS
CYT. C LOSS FROM MITO-
CHONDRIA Cyt C lost, binds APAF-1 CASPASES APAF-1 STIMULATES APOPTOSIS DNA DAMAGE P53
MITOCHONDRIAL PATH…WITH TROPHIC FACTOR PRESENT : MITOCHONDRIAL PATH…WITH TROPHIC FACTOR PRESENT TROPHIC FACTOR BINDS
RECEPTOR; TELLS CELL
NOT TO COMMIT SUICIDE BAD
OFF BAD NO LONGER INHIBITS BCL-2 BCL-2 PREVENTS CYTOCHROME C
MOVEMENT OUT OF MITOCHONDRIA;
APAF, CASPASE NOT STIMULATED NO APOPTOSIS MEMBRANE
VIEW APOPTOSIS ANIMATION; SEE COURSE WEB SITE : VIEW APOPTOSIS ANIMATION; SEE COURSE WEB SITE D:\cell biol 3611\apop cell signaling\apoptosis.mov
Slide67 : More fat (or less exercise), less apoptosis in cancer cells, more cancer.
Cancer cells know they are supposed to die by apoptosis, but somehow prevent the cell suicide p53
Slide68 : BCL-2 BAD CELL