Phospho-Raf1 (S43) Recombinant Rabbit Monoclonal Antibody [SD087-05]

Function

Several serine/threonine protein kinases have been implicated as intermediates in signal transduction pathways. These include ERK/MAP kinases, ribosomal S6 kinase (Rsk)and Raf-1. Raf-1 is a cytoplasmic protein with intrinsic serine/threonine activity. It is broadly expressed in nearly all cell lines tested to date and is the cellular homolog of v-Raf, the product of the transforming gene of the 3611 strain of murine sarcoma virus. The unregulated kinase activity of the v-Raf protein has been associated with transformation and mitogenesis while the activity of Raf-1 is normally suppressed by a regulatory N-terminal domain. Raf-1 is activated in response to activation of a variety of tyrosine kinase receptors as well as in response to pp60v-Src expression. There is accumulating evidence that Ras p21 may play a role in activation of Raf-1 and may play the role of the messenger from membrane tyrosine kinases to Raf-1.

Background References

1. Liu D et al. Sulfur dioxide inhibits vascular smooth muscle cell proliferation via suppressing the Erk/MAP kinase pathway mediated by cAMP/PKA signaling. Cell Death Dis 5:e1251 (2014).

2. De La Garza EM et al. Raf-1, a potential therapeutic target, mediates early steps in endometriosis lesion development by endometrial epithelial and stromal cells. Endocrinology 153:3911-21 (2012).

Sequence Similarity

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.

Tissue Specificity

In skeletal muscle, isoform 1 is more abundant than isoform 2.

Post-translational Modification

Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494 results in its activation. Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation. Phosphorylation at Ser-259 induces the interaction with YWHAZ and inactivates kinase activity. Dephosphorylation of Ser-259 by the complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves inactivation, leading to stimulate RAF1 activity. Phosphorylation at Ser-338 by PAK1 and PAK5 and Ser-339 by PAK1 is required for its mitochondrial localization. Phosphorylation at Ser-621 in response to growth factor treatment stabilizes the protein, possibly by preventing proteasomal degradation. Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells. Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338. Dephosphorylation at Ser-338 by PPP5C results in an activity decrease.; Methylated at Arg-563 in response to EGF treatment. This modification leads to destabilization of the protein, possibly through proteasomal degradation.

Subcellular Location

Cytoplasm, Cell membrane, Mitochondrion, Nucleus.

UNIPROT

SwissProt: P04049 Human

SwissProt: Q99N57 Mouse

SwissProt: P11345 Rat

Synonyms