Cell & Molecular - G-Protein

Cristabel Ruiz

Dr. Dunbar

Cell & Molecular

2/11/14

G-Proteins

        G – Proteins are used in many biological processes within the body. Their basic role is to bind specific ligands to the cell surface, such as hormones, neurotransmitters and transfer a signal from the outside of a cell into the inside of a cell. This allows the G protein to regulate systems within the body that control a biological response, by factors the bind to and hydrolyze the Guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When the G protein is activated it causes a cascade of further signaling events that results in a change in the cell function. G proteins are constantly dealt with incoming signals that are transferred to the appropriate target for a biological response.  

In this lecture, it focuses on a class of proteins that bind to GTP proteins that function as a molecular switch that can be reversible. The GTP binding proteins come in two forms; the GTP state is on, and the GDP state is off. The ras proteins are known to be low molecular weight G-proteins, because they bind to guanine nucleotides, GTP and GDP. The ras proteins function like a switch that consist of on and off states, by having a GTPase activity that converts the GTP to GDP by either adding or removing a phosphate through hydrolyzation. When passing a signal through the ras protein it depends on the balance between GTP and GDP within a cell. If the balance towards the GDP tips, it will inhibit a downstream signal, and reacts  the same way with GTP. These ras proteins are used as model, or prototype to learn how they are regulated.

Dr. Wittinghofer continues to explain the link between GTPases reactions and disease. In GTPases, the rho proteins functions as an on and off switch with GDP and GTP. The cell controls this switch by regulating the interconversion of the GTP and GDP. The guanine nucleotide exchange factors (GEFs) react with the exchange of GDP for GTP for activation, which allows it to recognize the downstream signal. The GTPase activating proteins (GAP) increase the activity of rho proteins that causes an inactivation. The Map kinase pathway explains how the signal travels through the cell. The growth factor binds to the cell membrane, then it bind to its growth factor receptor called RTK (receptor tyrosine kinase), the RTK gets phosphorylated and recruits the exchange factor called SoS. This then activates Ras to the GDP state, and the ras connects with downstream components of three different types of kinases. The Raf kinase is the starting kinase, then MEK and ERK kinase are interacting, which is apart of the MAP kinase pathway. Once the signal goes through the MAP kinase pathway, it goes into the nucleus and activates transcription.