What is the Difference Between GAP and GEF

The key difference between GAP and GEF is that GAP (GTPase activating protein) is a protein that can turn off downstream signalling of the cell after binding to G protein, while GEF (guanine nucleotide exchange factor) is a protein that can turn on downstream signalling of the cell after binding to G protein.

G proteins are also known as guanine nucleotide-binding proteins. A G protein is a protein that can act as a molecular switch inside the biological cell. It is involved in transmitting signals from a variety of stimuli outside a cell to the inside of a cell. Moreover, G proteins belong to a larger group of enzymes called GTPases. The activity of G protein is regulated by factors that control the ability of G protein to hydrolyze GTP to GDP. When G protein is bound to GTP, it is active. But when G protein is bound to GDP, it is inactive. Therefore, GAP and GEF are two factors that can regulate the function of G protein.

CONTENTS

1. Overview and Key Difference
2. What is GAP 
3. What is GEF
4. Similarities – GAP and GEF
5. GAP vs GEF in Tabular Form
6. Summary – GAP vs GEF

What is GAP?

GTPase activating protein (GAP) is a protein that can turn off downstream signalling the cell after binding to the G protein. This protein is also called the GTPase accelerating protein. It can bind to activated G proteins and stimulate their GTPase activity. This results in the termination of the downstream signalling events. GAP terminates the signalling events by inducing the GTP hydrolysis. When it enhances the GTP hydrolysis (GTP⇒GDP) reaction of the G protein, G protein ultimately binds with GDP. This inactivates G protein and turns off the downstream signalling.

In this sense, GAP function is opposite to that of the guanine nucleotide exchange factor (GEF), which enhances the G protein-mediated downstream signalling. GAP deregulation is often associated with cancers. This is due to either a loss of function of GAPs associated with G proteins or a loss of the G protein’s ability to respond to its GAP.

What is GEF?

Guanine nucleotide exchange factor (GEF) is a protein that can turn on downstream signalling of the cell after binding to G protein. It is a protein or a protein domain that is involved in the activation of small GTPases (G proteins). Normally, GDP dissociates from inactive G proteins very slowly. The binding of GEF to G protein catalyzes the dissociation of GDP, allowing a GTP molecule to bind in its place.

Moreover, the binding of GTP to the G protein molecule results in the release of GEF. Thus, it activates the G protein molecule and G protein-mediated downstream cell signalling. Furthermore, some GEFs can activate multiple G proteins while others are specific to a single G protein.

What are the Similarities Between GAP and GEF?

• GAP and GEF are two factors that can regulate the function of G protein.
• Both factors are proteins.
• These factors bind to G proteins or GTPases.
• Both factors can regulate downstream cell signalling
• Their roles are extremely important for cellular function.

What is the Difference Between GAP and GEF?

GAP is a protein that can turn off downstream signalling of the cell after binding to G protein while GEF is a protein that can turn on downstream signalling of the cell after binding to a G protein. Thus, this is the key difference between GAP and GEF. Furthermore, GAP enhances the GTP hydrolysis reaction of the G protein, while GEF enhances the dissociation of GDP from G protein.

The below infographic presents the differences between GAP and GEF in tabular form for side by side comparison.

Summary – GAP vs GEF

GAP and GEF are two factors that can regulate the downstream cell signalling of the cell after binding to G proteins. GAP is a protein that can turn off downstream signalling of the cell after binding to G protein, while GEF is a protein that can turn on downstream signalling of the cell after binding to G protein. So, this is the summary of the difference between GAP and GEF.

Reference:

1. “GTPase-Activating Protein.” An Overview | ScienceDirect Topics.
2. “Guanine Nucleotide Exchange Factor.” An Overview | ScienceDirect Topics.

Image Courtesy:

1. “Normal G protein activity” By Clareassis – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “ROCK protein function” By Cellular Biochemistry II – Own work (CC BY-SA 3.0) via Commons Wikimedia