1rrb

Structural highlights

Function

[RAF1_RAT] Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation (By similarity). Phosphorylates TNNT2/cardiac muscle troponin T.^{[1] [2]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Serine/threonine protein kinase

References

1. ↑ Pfleiderer P, Sumandea MP, Rybin VO, Wang C, Steinberg SF. Raf-1: a novel cardiac troponin T kinase. J Muscle Res Cell Motil. 2009;30(1-2):67-72. doi: 10.1007/s10974-009-9176-y. Epub, 2009 Apr 21. PMID:19381846 doi:http://dx.doi.org/10.1007/s10974-009-9176-y
2. ↑ Catling AD, Schaeffer HJ, Reuter CW, Reddy GR, Weber MJ. A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function. Mol Cell Biol. 1995 Oct;15(10):5214-25. PMID:7565670
3. ↑ Terada T, Ito Y, Shirouzu M, Tateno M, Hashimoto K, Kigawa T, Ebisuzaki T, Takio K, Shibata T, Yokoyama S, Smith BO, Laue ED, Cooper JA. Nuclear magnetic resonance and molecular dynamics studies on the interactions of the Ras-binding domain of Raf-1 with wild-type and mutant Ras proteins. J Mol Biol. 1999 Feb 12;286(1):219-32. PMID:9931261 doi:10.1006/jmbi.1998.2472