Ser338
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Home > Phosphorylation Site Page: > Ser338  -  RAF1 (mouse)

Site Information
RPRGQRDssyyWEIE   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447742

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 12 , 13 , 15 , 18 ) , electrophoretic mobility shift ( 12 ) , immunoprecipitation ( 2 , 3 ) , mass spectrometry ( 5 ) , mutation of modification site ( 2 , 3 , 7 , 10 , 12 , 15 , 18 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ) , phosphopeptide mapping ( 18 ) , western blotting ( 1 , 2 , 3 , 4 , 6 , 8 , 9 , 10 , 11 , 13 , 14 , 16 )
Disease tissue studied:
cervical cancer ( 4 ) , cervical squamous cell carcinoma ( 4 ) , leukemia ( 6 ) , chronic myelogenous leukemia ( 6 ) , neuroblastoma ( 11 )
Relevant cell line - cell type - tissue:
'brain, cerebral cortex' ( 8 ) , 'neuron, cortical'-brain ( 8 ) , 293 (epithelial) ( 1 , 3 , 10 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 10 , 14 , 17 , 18 ) , 3T3 (fibroblast) ( 15 ) , BaF3 ('B lymphocyte, precursor') ( 6 , 12 ) , brain ( 5 ) , BV-173 (myeloid) ( 6 ) , CaSki (cervical) ( 4 ) , COS (fibroblast) ( 15 , 16 , 18 ) , COS7 (fibroblast) ( 2 ) , E.coli (bacterial) ( 1 ) , embryo ( 5 ) , erythroid ( 12 ) , erythropoietic [EPOR (mouse)] ( 12 ) , HeLa (cervical) ( 4 ) , K562 (erythroid) ( 6 ) , liver ( 4 , 5 ) , lung ( 4 ) , MEF (fibroblast) [RAF1 (mouse), homozygous knockout] ( 7 , 9 ) , MEF (fibroblast) ( 2 ) , RAW 264 (macrophage) ( 13 ) , SiHa (squamous) ( 4 ) , SN56 (neuron) ( 11 )

Upstream Regulation
Regulatory protein:
APP (mouse) ( 8 ) , ERas (human) ( 3 ) , IL17RD (mouse) ( 14 ) , Merlin (mouse) ( 1 ) , RASA1 (mouse) ( 1 )
Putative in vivo kinases:
MEK1 (human) ( 3 ) , PAK1 (human) ( 10 )
Phosphatases, in vitro:
PPP2CB (human) ( 12 )
Treatments:
colforsin ( 10 , 15 ) , dasatinib ( 6 ) , EDTA ( 1 ) , EGF ( 2 , 3 , 10 , 15 , 16 , 18 ) , Epo ( 12 ) , estradiol ( 11 ) , FGF2 ( 14 ) , fibronectin ( 10 ) , GNF2 ( 6 ) , GW_5074 ( 13 ) , H-89 ( 10 ) , IBMX ( 10 , 15 ) , imatinib ( 6 ) , IPA-3 ( 3 ) , KN-93 ( 3 ) , LY294002 ( 17 ) , manumycin_A ( 13 ) , nilotinib ( 6 ) , PD98059 ( 3 ) , PDGF ( 1 , 15 , 17 , 18 ) , peptidoglycan ( 13 ) , phorbol_ester ( 16 , 18 ) , PLX4720 ( 3 ) , serum ( 16 ) , U0126 ( 3 ) , wortmannin ( 17 )

Downstream Regulation
Effects of modification on RAF1:
activity, induced ( 6 ) , enzymatic activity, induced ( 10 , 12 , 18 ) , molecular association, regulation ( 1 , 2 , 6 ) , phosphorylation ( 3 )
Effects of modification on biological processes:
apoptosis, inhibited ( 6 ) , carcinogenesis, induced ( 4 , 6 ) , cell growth, induced ( 6 ) , cell motility, induced ( 4 ) , signaling pathway regulation ( 6 )
Induce interaction with:
ROCK2 (mouse) ( 2 )
Inhibit interaction with:
RAF1 (human) ( 6 ) , RASA1 (mouse) ( 1 )

References 

1

Cui Y, et al. (2019) The NF2 tumor suppressor merlin interacts with Ras and RasGAP, which may modulate Ras signaling. Oncogene
31312020   Curated Info

2

Varga A, et al. (2017) RAF1/BRAF dimerization integrates the signal from RAS to ERK and ROKα. Sci Signal 10
28270557   Curated Info

3

Hu J, et al. (2013) Allosteric activation of functionally asymmetric RAF kinase dimers. Cell 154, 1036-46
23993095   Curated Info

4

Chiu CF, et al. (2012) Recombinant viral capsid protein VP1 suppresses migration and invasion of human cervical cancer by modulating phosphorylated prohibitin in lipid rafts. Cancer Lett 320, 205-14
22388104   Curated Info

5

Stokes MP, et al. (2012) PTMScan Direct: Identification and Quantification of Peptides from Critical Signaling Proteins by Immunoaffinity Enrichment Coupled with LC-MS/MS. Mol Cell Proteomics 11, 187-201
22322096   Curated Info

6

Packer LM, et al. (2011) Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic myeloid leukemia. Cancer Cell 20, 715-27
22169110   Curated Info

7

Mielgo A, et al. (2011) A MEK-independent role for CRAF in mitosis and tumor progression. Nat Med 17, 1641-5
22081024   Curated Info

8

Echeverria V, et al. (2008) Raf inhibition protects cortical cells against beta-amyloid toxicity. Neurosci Lett 444, 92-6
18706973   Curated Info

9

Noble C, et al. (2008) CRAF autophosphorylation of serine 621 is required to prevent its proteasome-mediated degradation. Mol Cell 31, 862-72
18922468   Curated Info

10

Edin ML, Juliano RL (2005) Raf-1 serine 338 phosphorylation plays a key role in adhesion-dependent activation of extracellular signal-regulated kinase by epidermal growth factor. Mol Cell Biol 25, 4466-75
15899852   Curated Info

11

Guerra B, Díaz M, Alonso R, Marin R (2004) Plasma membrane oestrogen receptor mediates neuroprotection against beta-amyloid toxicity through activation of Raf-1/MEK/ERK cascade in septal-derived cholinergic SN56 cells. J Neurochem 91, 99-109
15379891   Curated Info

12

Chen C, Sytkowski AJ (2004) Erythropoietin regulation of Raf-1 and MEK: evidence for a Ras-independent mechanism. Blood 104, 73-80
15026317   Curated Info

13

Chen BC, et al. (2004) Peptidoglycan induces nuclear factor-kappaB activation and cyclooxygenase-2 expression via Ras, Raf-1, and ERK in RAW 264.7 macrophages. J Biol Chem 279, 20889-97
15007072   Curated Info

14

Kovalenko D, et al. (2003) Sef inhibits fibroblast growth factor signaling by inhibiting FGFR1 tyrosine phosphorylation and subsequent ERK activation. J Biol Chem 278, 14087-91
12604616   Curated Info

15

Dumaz N, Light Y, Marais R (2002) Cyclic AMP blocks cell growth through Raf-1-dependent and Raf-1-independent mechanisms. Mol Cell Biol 22, 3717-28
11997508   Curated Info

16

Dhillon AS, et al. (2002) Regulation of Raf-1 activation and signalling by dephosphorylation. EMBO J 21, 64-71
11782426   Curated Info

17

Chiloeches A, Mason CS, Marais R (2001) S338 phosphorylation of Raf-1 is independent of phosphatidylinositol 3-kinase and Pak3. Mol Cell Biol 21, 2423-34
11259591   Curated Info

18

Mason CS, et al. (1999) Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf activation. EMBO J 18, 2137-48
10205168   Curated Info