RRAS2: Related RAS viral (r-ras) human oncogene homolog 2
PDB Code: 2ERY
Cells respond in many ways to environmental changes including altering gene expression, physically moving locations, changes to cell-cell interactions, differentiation and even altering their life spans. This is achieved through a signalling network that consists of several signalling pathways. The network receives multiple signals, interprets the signals, amplified and then transmits the signals. One of the best characterised signalling pathways involves the ras GTPase family. The importance of this family of small GTPases to human health was first recognised through the identification of the human H-Ras, N-Ras and K-Ras genes as being oncogenic.
RRAS2 (TC21) has been identified from expression cDNA libraries generated from either a human teratocarcinoma or an ovarian carcinoma cell line as a potent transforming gene. The mutation (Gln72Leu) is the equivalent mutation that was previously identified in H-ras, N-ras and K-ras. Another mutant form of RRAS2 from a uterine leiomyosarcoma cell line, resulted in the insertion of three amino acids after codon position 24 thus producing a constitutively active state.
Even though RRAS2 and Ras show indistinguishable biological activities the signalling pathways between these structurally similar proteins are different. The classical Ras pathway involves the activation of the Raf-1 Ser/Thr kinase pathway whereas RRAS2 stimulates the PI3-kinase pathway.
Viral-induced lymphomas identidied RRAS2A as the gene whose transcription was upregulated most frequently. RRAS2A is also upregulated in esophageal tumor formation and may be useful as a clinical marker for the disease.
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