Question

1. Understand the role of each in cell signaling:
   • GTPase RAS and MAP kinase

Answer 1

Role of RAS GTPases and MAP Kinase in cell signalling

G proteins are part of or coupled to cell surface receptors called G protein coupled receptors. The receptor has extra cellular domain to bind with land, while intracellular domain bind to G protein. This G protein is a molecular switch with 3 subunits namely alpha beeta nad gamma. the alpha subunit has intrinsic GTPAse activity . This is important because GTPases are superfamily of enzyme that act as molecular switches and regulate the cellular response. The GTP ases regulate the signalling pathway by alteration between active GTP bound and inactive GDP bound state. When bind with GTP they are ON and when bind with GDP they are off. This was facilitated by GEFs (Guanine exchange factor) which cause exchanging GDP to GTP thus activating G protein and GAPs (GTPase activating proteins) that stimulate GTP hydrolysis thus inactivating G proteins.

RAS is an intracellular switch, a monomeric G protein which have important role in signal trasduction involved in cell proliferation and differentiation. RAS performs its function in GTP bound state and turns off at GDP bound state after performing its function. Activated Ras (Ras GTP) lead to a cascade of reaction in that Raf ,MEK and MAP kinases are phosphorylated and activated in a sequential manner. Activated MAP kinasaes transported into nucleus.MAP kinases are activated by stimuli such as growth factors and mitogens. And as a result the activated MAP kinase regulate activity of transcription factors controlling cell division.

Ras mutation leads to cancer as it cause uncontrolled cell proliferation.

MAP kinases phosphorylate more than 150 proteins ( in nuclues and cytoplasm), some of which are regulators of gene expression.