Product Name: Raf1 (298-305) pS301+pT303
Product Number: PE-04AHS90
Size: 200 µg      Price:57.00
1 mg      $US113.00
Peptide Name: Raf1 (298-305) pS301+pT303

Product Use: Services as a blocking peptide for use with the Raf1-pS301+pT303 rabbit polyclonal antibody (Cat. No.: AB-PK792) that is also available from Kinexus. This phosphopeptide may also be useful as a substrate for screening the phosphatase activity of protein phosphatases. The peptide sequence is located in the region between the C1_1 and kinase catalytic domains. This is the major in vivo phosphorylation sites in Raf1. Phosphorylation inhibits phosphotransferase activity, inhibits interaction with H-Ras-1, and regulates intracellular location.

Peptide Production Method: Solid-phase peptide synthesis

Peptide Origin: Homo sapiens

Peptide Sequence: NNL-pS-P-pT-GW

Peptide Modifications N Terminus: Free amino

Peptide Modifications C Terminus: βAla-Cys

Peptide Modifications Other: Phosphorylated

Peptide Molecular Mass Calculated: 1221.12 Da

Peptide Purity Percent after Synthesis and Purification: >90

Peptide Appearance: White powder

Peptide Form: Solid

Storage Conditions: -20°C

Related Product 1: Raf1 - pS301+pT303 phosphosite-specific antibody (Cat. No.: AB-PK792)

Scientific Background: Raf1 (c-Raf) is a protein-serine/threonine kinase of the TKL group and RAF family. It links signalling from activated membrane-associated Ras GTPases with the MAPK/ERK intracellular signalling cascade to control the differentiation, proliferation, survival, apoptosis, and oncogenic transformation of cells. Raf1 has anti-apoptotic functions through its phosphorylation of S75 of the BAD/Bcl2-antagonist of cell death. Bcl2 then targets Raf1 to the mitochondria and once activated, Raf1 enhances Bcl2 mediated apoptotic resistance. Raf1 is activated by direct binding to Ras isforms and phosphorylation at S338, S339, Y340, Y341, S471, T481, T491, S494, S497, S499 and S621. Phosphorylation of S471 induces interaction with MEK1, and. phosphorylation at S621 induces interaction with 14-3-3-zeta. Phosphorylation at S233 and S289 inhibits interaction with H-Ras-1 and increases interaction with 14-3-3 beta. Phosphorylation at S259 inhibits phosphotransferase activity, reduces H-Ras-1 and PPP2CB binding, and induces binding of 14-3-3-beta and zeta. It also appears to necessary for PKC-alpha activation of Raf1. Phosphorylation of S43, S296, S301 and S642 inhibits phosphotransferase activity and inhibits interaction with H-Ras-1. Phosphorylation of Y341 inhibits interaction with Raf1. Raf1 appears to be an oncoprotein (OP), and cancer-related mutations in human tumours point to a gain of function of the protein kinase. Overactive Raf-1 kinase phosphotransferase activity due to different mutations has been implicated in the pathogenesis of both Noonan and Leopard syndromes. Substitution mutations are also associated with other cancers. Inhibition of Raf1 phosphotransferase activity by the protein phosphatase PPP5C is impaired (no binding) with S338D and S339E mutations when these occur in conjunction with phosphomimetic Y340D and Y341D mutations in Raf1. This results in a constitutively active kinase, and extensive phosphorylation of S338. The T491D and T494D can increase kinase phosphotransferase activity but the kinase is still sensitive to PPP5C. Methylation of Raf1 can be inhibited with a R563K mutation, leading to increased stability and catalytic activity. Raf1 is also upregulated in many cancers, since Ras (an upstream activator of RAF) is mutated/upregulated in many cancers. For example, Raf1 is over-expressed due to oncogenic ras mutations in about 35% of Non-Small Cell Lung Cancer (NSCLC). A small number of Raf mutations have been found in stomach and mouth tumours.