Ras GTPase

Ras GTPase is a family of proteins involved in transmitting signals within cells (cellular signal transduction). These proteins are a subfamily of the small GTPase superfamily and are involved in various cellular processes, including growth, differentiation, and survival. Ras proteins are often referred to as molecular switches because they cycle between an active GTP-bound state and an inactive GDP-bound state.

Structure

Ras proteins are small, approximately 21 kDa, and consist of a single polypeptide chain. They have a highly conserved structure that includes a GTP-binding domain and a C-terminal hypervariable region. The GTP-binding domain is responsible for the protein's ability to bind and hydrolyze GTP, while the hypervariable region is involved in membrane localization and interaction with other proteins.

Function

Ras proteins play a crucial role in the MAPK/ERK pathway, which is a key signaling pathway that regulates cell division, differentiation, and apoptosis. When Ras is activated by binding to GTP, it interacts with and activates a series of downstream effectors, including Raf kinase, PI3K, and RalGDS. These interactions lead to the activation of various signaling cascades that ultimately result in changes in gene expression and cellular behavior.

Regulation

Ras activity is tightly regulated by two main types of proteins: guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). GEFs promote the exchange of GDP for GTP, thereby activating Ras, while GAPs increase the intrinsic GTPase activity of Ras, leading to its inactivation.

Clinical Significance

Mutations in Ras genes are among the most common genetic alterations in human cancers. These mutations often result in constitutively active Ras proteins that drive uncontrolled cell proliferation and tumorigenesis. The most frequently mutated Ras genes in cancer are HRAS, KRAS, and NRAS. Targeting Ras signaling pathways is a major focus of cancer research and drug development.

History

The Ras gene was first identified in the early 1980s as an oncogene in rat sarcoma virus. Subsequent research revealed its role in normal cellular signaling and its involvement in human cancers. The discovery of Ras and its function in cell signaling has been pivotal in understanding the molecular basis of cancer.

Also see

• MAPK/ERK pathway
• GTPase-activating protein
• Guanine nucleotide exchange factor
• Oncogene
• Signal transduction

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