What is KRAS4b?

What is KRAS4b?

KRAS4b is the primary isoform in human cells and is post-translationally modified via the CaaX prenylation pathway to permit its interaction with the plasma membrane where much of the signaling process occurs (Figs 1a).

Where does prenylation occur?

Protein prenylation occurs only in eucaryotes and is of particular interest because it is found in proteins involved in signal transduction pathways that regulate critical cellular functions including cell growth and proliferation. The enzyme Ras is farnesylated and is an example of such a protein.

What is a prenyl chain?

Prenylation is the covalent attachment of a lipid consisting of either three (farnesyl) or four (geranylgeranyl) isoprene units to a free thiol of a cysteine side chain at or near the C-terminus of a protein. From: Comprehensive Natural Products II, 2010.

What are HRAS NRAS and KRAS?

H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B).

What is the Prenylation process?

Prenylation is a multistep enzymatic process of adding hydrophobic prenyl moieties to proteins. Prenylation facilitates the attachment of these proteins to the cell membrane.

How does Prenylation affect proteins?

Prenylation serves as the first critical step for membrane targeting and binding, as well as mediating protein–protein interactions of a large number of these proteins; heterotrimeric G-proteins also require prenylation for activity.

What is the purpose of Farnesylation?

Farnesylation is a type of protein prenylation, where a 15-carbon farnesyl lipid group is transferred onto one or more C-terminal cysteine residues (Zhang and Casey, 1996). A subset of membrane proteins is farnesylated, making the C terminus more hydrophobic, facilitating their membrane binding.

Where does protein Lipidation occur?

1). Protein lipidation of molecules destined for secretion occurs in the lumen of organelles within the secretory pathway. Glycosylphosphatidylinositol (GPI) anchors attached to proteins in the endoplasmic reticulum tether proteins to the extracellular face of the plasma membrane.

What does K stands for in KRAS?

KRAS (Kirsten rat sarcoma virus) is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway.

Why is Prenylation important?

  • October 16, 2022