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By: Khuram aziz   Cell signaling:  Communication Between Cells and Their Environment Study hard and stay focused on your educational goals. But always have a backup plan! Remember: while chance favors the prepared mind,  you can’t always be where the lighting strikes. Overview of intracellular signaling:  Initiation and responses
What are G-proteins? ,[object Object],[object Object],[object Object],Fig.  15.1 Examples of GTPase proteins Ras, Cdc-42 (hormone, GF, drug)
GTPases and disease. ,[object Object],[object Object],[object Object]
G-proteins are tightly regulated ,[object Object],[object Object],[object Object],[object Object]
The heterotrimeric G proteins transmit signals from a variety of cell surface   receptors to enzymes and channels  ,[object Object],[object Object],[object Object],[object Object]
Fig 15.3  The G Protein Cycle
GTP is very small and can diffuse rapidly throughout the cell ,[object Object],[object Object],Minireview Translocation and Reversible Localization of Signaling Proteins: A Dynamic Future for Signal Transduction Mary N. Teruel    1  and Tobias Meyer    1 1  Department of Molecular Pharmacology, Stanford University Medical School, 269 Campus Drive, Stanford, California 94305
GTP binds to GTPases.  Hold on! ,[object Object],[object Object],[object Object]
Rabs are members of the small G-protein family ,[object Object],[object Object],[object Object]
Other G Proteins ,[object Object],[object Object],[object Object],[object Object],[object Object]
Ras Activation and the MAP Kinase Cascade Raf-1 (Map kinase kinase kinase) MEK (MAP kinase kinase) ERK (MAP kinase) Tyrosine Kinases, G-Protein coupled receptors Nuclear regulatory proteins Cytoplasmic substrates See Fig. 15.2
What does Ras interact with? Raf
G proteins ,[object Object],[object Object]
Why do we care about the structure of the structure of G proteins: including the G   and G   interface? ,[object Object],[object Object],[object Object],[object Object],[object Object],Fig. 15.11
The regulation of G proteins. Fig. 15.12
A Ribbon Diagram of the G   ,[object Object],[object Object]
A Schematic of the G   Propeller Structure ,[object Object],Each propeller has 4   -sheets
Take Home Message #1. Cells maintain their signaling outputs by establishing a balance between the nucleotide exchange rate and the hydrolysis rate ,[object Object]
Answer:  G-GDP ,[object Object],[object Object],[object Object]
Why do we need GAPs? ,[object Object]
Answer ,[object Object]
Take home message #2 Hydrolysis is the turn-off signal   that induces heterotrimeric G protein    subunits (G      ) to disengage their effectors.  Note change in structure of  GTP versus GDP bound G protein
Why do we need GEFs?
Answer ,[object Object]
Do you remember everything from yesterday’s lecture? If you say yes, you get a donut! If not, then you need to pay attention to the CREB story.   Fact: CREB: cAMP response element binding protein.  Binds to DNA at the CRE (cAMP Response  Element) and activates transcription.
What does CREB do? ,[object Object]
Can eating CREB make you smart?  No But eating donuts can make you happy, and happiness is good psychological health! ,[object Object]
cAMP is generated from ATP by an enzyme: adenylyl cyclase.  AC is regulated by G proteins
cAMP activates one or more kinases.  What are phosphatases?
Activation of cAMP and Protein Kinase A also play major roles in response of liver to glucagon or epinephrine. Figure 15.7
Thursday, IP3, Calcium and Receptor tyrosine kinases ,[object Object]
Regulation of PIP2 and PIP3 Synthesis Green arrows denote stimulatory effects; blue arrows denote synthetic pathways; red denotes inhibitory effect. Feedback inhibitory loop (1). Cross-talk between receptor signaling pathways (2). Feed-forward loop (3).
Plasma Membrane Functions that Require  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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G protein signal

  • 1. By: Khuram aziz Cell signaling: Communication Between Cells and Their Environment Study hard and stay focused on your educational goals. But always have a backup plan! Remember: while chance favors the prepared mind, you can’t always be where the lighting strikes. Overview of intracellular signaling: Initiation and responses
  • 2.
  • 3.
  • 4.
  • 5.
  • 6. Fig 15.3 The G Protein Cycle
  • 7.
  • 8.
  • 9.
  • 10.
  • 11. Ras Activation and the MAP Kinase Cascade Raf-1 (Map kinase kinase kinase) MEK (MAP kinase kinase) ERK (MAP kinase) Tyrosine Kinases, G-Protein coupled receptors Nuclear regulatory proteins Cytoplasmic substrates See Fig. 15.2
  • 12. What does Ras interact with? Raf
  • 13.
  • 14.
  • 15. The regulation of G proteins. Fig. 15.12
  • 16.
  • 17.
  • 18.
  • 19.
  • 20.
  • 21.
  • 22. Take home message #2 Hydrolysis is the turn-off signal that induces heterotrimeric G protein   subunits (G    ) to disengage their effectors. Note change in structure of GTP versus GDP bound G protein
  • 23. Why do we need GEFs?
  • 24.
  • 25. Do you remember everything from yesterday’s lecture? If you say yes, you get a donut! If not, then you need to pay attention to the CREB story. Fact: CREB: cAMP response element binding protein. Binds to DNA at the CRE (cAMP Response Element) and activates transcription.
  • 26.
  • 27.
  • 28. cAMP is generated from ATP by an enzyme: adenylyl cyclase. AC is regulated by G proteins
  • 29. cAMP activates one or more kinases. What are phosphatases?
  • 30. Activation of cAMP and Protein Kinase A also play major roles in response of liver to glucagon or epinephrine. Figure 15.7
  • 31.
  • 32. Regulation of PIP2 and PIP3 Synthesis Green arrows denote stimulatory effects; blue arrows denote synthetic pathways; red denotes inhibitory effect. Feedback inhibitory loop (1). Cross-talk between receptor signaling pathways (2). Feed-forward loop (3).
  • 33.