Phospho-Raf1 (S621) Recombinant Rabbit Monoclonal Antibody [JJ085-05] (ET1701-3)

UNIPROT #

P04049

PROTEIN NAME

Phospho-Raf1 (S621)

SYNONYMS

c Raf antibody;C-raf antibody;C-Raf proto-oncogene, serine/threonine kinase antibody;CMD1NN antibody;Craf 1 transforming gene antibody;cRaf antibody;Craf1 transforming gene antibody;EC 2.7.11.1 antibody;kinase Raf1 antibody;Murine sarcoma 3611 oncogene 1 antibody;NS5 antibody;Oncogene MIL antibody;Oncogene RAF1 antibody;OTTHUMP00000160218 antibody;OTTHUMP00000207813 antibody;OTTHUMP00000209389 antibody;Protein kinase raf 1 antibody;Proto-oncogene c-RAF antibody;Raf 1 antibody;Raf 1 proto oncogene serine/threonine kinase antibody;RAF antibody;Raf proto oncogene serine/threonine protein kinase antibody;RAF proto-oncogene serine/threonine-protein kinase antibody;RAF-1 antibody;RAF1 antibody;RAF1_HUMAN antibody;Similar to murine leukemia viral (V-raf-1) oncogene homolog 1 antibody;TRANSFORMING REPLICATION-DEFECTIVE MURINE RETROVIRUS 3611-MSV antibody;v raf 1 murine leukemia viral oncogene homolog 1 antibody;v-raf murine sarcoma viral oncogene homolog 1 antibody;v-raf-1 murine leukemia viral oncogene-like protein 1 antibody;vraf1 murine leukemia viral oncogene homolog 1 antibody

SEQUENCE SIMILARITIES

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.

FUNCTION

Raf-1 is a ubiquitously expressed cytoplasmic protein with intrinsic serine/threonine kinase activity. Raf-1, or c-Raf, 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 is associated with cellular transformation and mitogenesis. Raf-1 is normally suppressed by its regulatory N-terminal domain. Raf-1 is activated in response to a variety of tyrosine kinase receptors as well as in response to pp60v-Src expression. Specifically, Raf-1 is phosphorylated in the catalytic domain at Ser 338 and, to a lesser extent, Ser 339. This phosphorylation requires the co-activation of PI 3-kinase and the Ras signaling pathway. Raf-1 is also phosphorylated on Tyr 340 and 341, which induces the phosphorylation of MEK. Phosphorylation of Ser 621 is essential for the catalytic activity of Raf-1 and downregulation by c-AMP-dependent protein kinase A (PKA). PKA also phosphorylates Raf-1 on Ser 43 and Ser 259. PKA phosphorylation of Ser 259 inhibits Raf-1 and decreases the phosphorylation necessary for Raf-1 activation at Ser 338.