Product Pathways - MAPK Signaling
Phospho-c-Raf (Ser338) (56A6) Rabbit mAb #9427
|W||H M R Mk||Endogenous||74||Rabbit IgG|
Reactivity Key: H=Human M=Mouse R=Rat Mk=Monkey
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.
Specificity / Sensitivity
Phospho-c-Raf (Ser338) (56A6) Rabbit mAb detects endogenous levels of c-Raf only when phosphorylated at Ser338.
Source / Purification
Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding serine 338 of human Raf.
A-Raf, B-Raf, and c-Raf (Raf-1) are the main effectors recruited by GTP-bound Ras to activate the MEK-MAP kinase pathway (1). Activation of c-Raf is the best understood and involves phosphorylation at multiple activating sites including Ser338, Tyr341, Thr491, Ser494, Ser497, and Ser499 (2). p21-activated protein kinase (PAK) has been shown to phosphorylate c-Raf at Ser338 and the Src family phosphorylates Tyr341 to induce c-Raf activity (3,4). Ser338 of c-Raf corresponds to similar sites in A-Raf (Ser299) and B-Raf (Ser445), although this site is constitutively phosphorylated in B-Raf (5). Inhibitory 14-3-3 binding sites on c-Raf (Ser259 and Ser621) can be phosphorylated by Akt and AMPK, respectively (6,7). While A-Raf, B-Raf, and c-Raf are similar in sequence and function, differential regulation has been observed (8). Of particular interest, B-Raf contains three consensus Akt phosphorylation sites (Ser364, Ser428, and Thr439) and lacks a site equivalent to Tyr341 of c-Raf (8,9). Research studies have shown that the B-Raf mutation V600E results in elevated kinase activity and is commonly found in malignant melanoma (10). Six residues of c-Raf (Ser29, Ser43, Ser289, Ser296, Ser301, and Ser642) become hyperphosphorylated in a manner consistent with c-Raf inactivation. The hyperphosphorylation of these six sites is dependent on downstream MEK signaling and renders c-Raf unresponsive to subsequent activation events (11).
- Avruch, J. et al. (1994) Trends Biochem. Sci. 19, 279-283.
- Chong, H. et al. (2001) EMBO J. 20, 3716-3727.
- King, A.J. et al. (1998) Nature 396, 180-183.
- Fabian, J.R. et al. (1993) Mol. Cell Biol. 13, 7170-7179.
- Mason, C.S. et al. (1999) EMBO J. 18, 2137-2148.
- Zimmermann, S. and Moelling, K. (1999) Science 286, 1741-1744.
- Sprenkle, A.B. et al. (1997) FEBS Lett. 403, 254-258.
- Marais, R. et al. (1997) J. Biol. Chem. 272, 4378-4383.
- Guan, K.L. et al. (2000) J. Biol. Chem. 275, 27354-27359.
- Davies, H. et al. (2002) Nature 417, 949-954.
- Dougherty, M.K. et al. (2005) Mol. Cell 17, 215-224.
- Kajiya, M. et al. (2008) J Biol Chem 283, 16259-67. Applications: Western Blotting
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- 7003 20X LumiGLO® Reagent and 20X Peroxide
Rabbit Monoclonals Produced Using Epitomics® Technology, U.S. Patent No. 5,675,063.
For Research Use Only. Not For Use In Diagnostic Procedures.