Ser706

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Phosphorylation Site Page:

Ser706 - CD44 (human)

Site Information

LNGEASKsQEMVHLV SwissProt Entrez-Gene

Predicted information: Scansite

Orthologous residues: CD44 (mouse): S742, CD44 (rat): S467, CD44 iso2 (mouse): S327

Blast this site against: NCBI SwissProt PDB

Available spectra: 1 CST

In vivo Characterization

Methods used to characterize site in vivo:	[32P] bio-synthetic labeling (43, 44, 45, 46), immunoprecipitation (11), mass spectrometry (3, 4, 7, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 27, 28, 29, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42), mutation of modification site (1, 43, 45, 46), phospho-antibody (5, 7, 11, 30, 43, 44), phosphoamino acid analysis (45), western blotting (1, 5, 7, 11)
Disease tissue studied:	brain cancer (29, 42), glioblastoma (29, 42), glioma (29, 42), cervical cancer (10), cervical adenocarcinoma (10), lung cancer (7, 23), non-small cell lung cancer (23), prostate cancer (11)
Relevant cell line - cell type - tissue:	293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] (8), 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] (43), CL1-0 (pulmonary) (7), CL1-1 (pulmonary) (7), CL1-2 (pulmonary) (7), CL1-5 (pulmonary) (7), COS (fibroblast) (1, 46), Flow2000 (30), GM00130 (B lymphocyte) (9), GM00200 (fibroblast) (32, 33), GM18366 (fibroblast) (34, 35), HeLa (cervical) (3, 4, 15, 16, 17, 18, 25, 27, 28, 31), HeLa S3 (cervical) (10, 24), HT1080 (fibroblast) (44), M059J (glial) (41, 42), M059K (glial) (29, 36, 37, 38, 39, 40), MDA-MB468 (breast cell) (30), MKN-45 (gastric) (21, 22), NCI-H1299 (pulmonary) (23), NCI-H2228 (pulmonary) (14), NCI-H3255 (pulmonary) (12, 13), osteoclast (5), PC3 (prostate cell) (11), RPM-MC (melanocyte) (43, 44, 45), T lymphocyte-blood (19), TERT20 ('stem, mesenchymal') (26)

Controlled by

Putative upstream kinases:	CaMK2-alpha (human) (44)
Kinases, in vitro:	CaMK2-alpha (human) (44)
Treatments:	bisindolylmaleimide (30), cAMP analog (30), H-89 (30), hyaluronan (5), ionizing radiation (9), KN-93 (44), metastatic potential (7), nocodazole (10), phorbol ester (30, 43), UV (29)

Downstream Regulation

Effects of modification on CD44:	activation (45), intracellular localization (1, 46), molecular association, regulation (11)
Effects of modification on biological processes:	cell motility, altered (11), transcription, induced (1)
Inhibit interaction with:	MMP9 (human) (11)

	References

1	Ildefonso CJ, et al. (2012) The Liberation of CD44 Intracellular Domain Modulates Adenoviral Vector Transgene Expression. J Biol Chem 287, 32697-707 22865879 Curated Info
2	Weber C, Schreiber TB, Daub H (2012) Dual phosphoproteomics and chemical proteomics analysis of erlotinib and gefitinib interference in acute myeloid leukemia cells. J Proteomics 75, 1343-56 22115753 Curated Info
3	(2011) CST Curation Set: 11709; Year: 2011; Biosample: HeLa; Disease: cervical adenocarcinoma; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-ATM/ATR Substrate (SQ) (D23H2/D69H5) Rabbit mAb Cat#: 9607, PTMScan(R) Phospho-ATM/ATR Substrate (SQ) Immunoaffinity Beads Cat#: 9884 Curated Info
4	(2011) CST Curation Set: 11710; Year: 2011; Biosample: HeLa; Disease: cervical adenocarcinoma; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-ATM/ATR Substrate (SQ) (D23H2/D69H5) Rabbit mAb Cat#: 9607, PTMScan(R) Phospho-ATM/ATR Substrate (SQ) Immunoaffinity Beads Cat#: 9884 Curated Info
5	Pivetta E, et al. (2011) Blood-derived human osteoclast resorption activity is impaired by Hyaluronan-CD44 engagement via a p38-dependent mechanism. J Cell Physiol 226, 769-79 20799279 Curated Info
6	Rigbolt KT, et al. (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal 4, rs3 21406692 Curated Info
7	Wang YT, et al. (2010) An informatics-assisted label-free quantitation strategy that depicts phosphoproteomic profiles in lung cancer cell invasion. J Proteome Res 9, 5582-97 20815410 Curated Info
8	Christensen GL, et al. (2010) Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. Mol Cell Proteomics 9, 1540-53 20363803 Curated Info
9	Bennetzen MV, et al. (2010) Site-specific phosphorylation dynamics of the nuclear proteome during the DNA damage response. Mol Cell Proteomics 9, 1314-23 20164059 Curated Info
10	Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3 20068231 Curated Info
11	Desai B, Ma T, Zhu J, Chellaiah MA (2009) Characterization of the expression of variant and standard CD44 in prostate cancer cells: identification of the possible molecular mechanism of CD44/MMP9 complex formation on the cell surface. J Cell Biochem 108, 272-84 19582779 Curated Info
12	(2009) CST Curation Set: 7323; Year: 2009; Biosample: NCI-H3255; Disease: non-small cell lung cancer; Treatment: untreated; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-RXX(s/t)(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) PKD Substrate Antibody Cat#: 4381, PTMScan(R) Phospho-PKD Substrate Motif (LXRXXpS/pT) Immunoaffinity Beads Cat#: 1986 Curated Info
13	(2009) CST Curation Set: 7322; Year: 2009; Biosample: NCI-H3255; Disease: non-small cell lung cancer; Treatment: untreated; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-RXX(s/t)(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) PKD Substrate Antibody Cat#: 4381, PTMScan(R) Phospho-PKD Substrate Motif (LXRXXpS/pT) Immunoaffinity Beads Cat#: 1986 Curated Info
14	(2009) CST Curation Set: 7320; Year: 2009; Biosample: NCI-H2228; Disease: non-small cell lung cancer; Treatment: untreated; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-RXX(s/t)(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) PKD Substrate Antibody Cat#: 4381, PTMScan(R) Phospho-PKD Substrate Motif (LXRXXpS/pT) Immunoaffinity Beads Cat#: 1986 Curated Info
15	(2009) CST Curation Set: 6246; Year: 2009; Biosample: HeLa; Disease: cervical adenocarcinoma; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980 Curated Info
16	(2009) CST Curation Set: 6247; Year: 2009; Biosample: HeLa; Disease: cervical adenocarcinoma; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980 Curated Info
17	(2009) CST Curation Set: 6241; Year: 2009; Biosample: HeLa; Disease: cervical adenocarcinoma; Treatment: nocodazole; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980 Curated Info
18	(2009) CST Curation Set: 6240; Year: 2009; Biosample: HeLa; Disease: cervical adenocarcinoma; Treatment: nocodazole; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980 Curated Info
19	Carrascal M, et al. (2008) Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment. J Proteome Res 7, 5167-76 19367720 Curated Info
20	(2008) CST Curation Set: 5534; Year: 2008; Biosample: MGH lung 14T; Disease: non-small cell lung cancer; Treatment: untreated; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-pTyr Antibody Used to Purify Peptides prior to MS2: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
21	(2008) CST Curation Set: 5568; Year: 2008; Biosample: MKN-45; Disease: gastric carcinoma; Treatment: Su11274; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980 Curated Info
22	(2008) CST Curation Set: 5569; Year: 2008; Biosample: MKN-45; Disease: gastric carcinoma; Treatment: Su11274; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980 Curated Info
23	Tsai CF, et al. (2008) Immobilized metal affinity chromatography revisited: pH/acid control toward high selectivity in phosphoproteomics. J Proteome Res 7, 4058-69 18707149 Curated Info
24	Daub H, et al. (2008) Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell 31, 438-48 18691976 Curated Info
25	Dephoure N, et al. (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 105, 10762-7 18669648 Curated Info
26	Thingholm TE, et al. (2008) TiO2-Based Phosphoproteomic Analysis of the Plasma Membrane and the Effects of Phosphatase Inhibitor Treatment. J Proteome Res 7, 3304-3313 18578522 Curated Info
27	(2008) CST Curation Set: 4706; Year: 2008; Biosample: HeLa; Disease: cervical adenocarcinoma; Treatment: untreated; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980 Curated Info
28	(2008) CST Curation Set: 4707; Year: 2008; Biosample: HeLa; Disease: cervical adenocarcinoma; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980 Curated Info
29	Stokes MP, et al. (2007) Profiling of UV-induced ATM/ATR signaling pathways. Proc Natl Acad Sci U S A 104, 19855-60 18077418 Curated Info
30	Tzircotis G, Thorne RF, Isacke CM (2006) Directional sensing of a phorbol ester gradient requires CD44 and is regulated by CD44 phosphorylation. Oncogene 25, 7401-10 16785995 Curated Info
31	Olsen JV, et al. (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635-48 17081983 Curated Info
32	(2006) CST Curation Set: 1772; Year: 2006; Biosample: GM00200; Disease: -; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
33	(2006) CST Curation Set: 1773; Year: 2006; Biosample: GM00200; Disease: -; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
34	(2006) CST Curation Set: 1774; Year: 2006; Biosample: GM18366; Disease: Seckel syndrome; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
35	(2006) CST Curation Set: 1775; Year: 2006; Biosample: GM18366; Disease: Seckel syndrome; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
36	(2006) CST Curation Set: 1614; Year: 2006; Biosample: M059K; Disease: glioblastoma; Treatment: normal; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
37	(2006) CST Curation Set: 1615; Year: 2006; Biosample: M059K; Disease: glioblastoma; Treatment: normal; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
38	(2006) CST Curation Set: 1616; Year: 2006; Biosample: M059K; Disease: glioblastoma; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
39	(2006) CST Curation Set: 1443; Year: 2006; Biosample: M059K; Disease: glioblastoma; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Curated Info
40	(2006) CST Curation Set: 1444; Year: 2006; Biosample: M059K; Disease: glioblastoma; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Curated Info
41	(2006) CST Curation Set: 1092; Year: 2006; Biosample: M059J; Disease: glioblastoma; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
42	(2005) CST Curation Set: 908; Year: 2005; Biosample: M059J; Disease: glioblastoma; Treatment: UV; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-(s/t)Q(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 Curated Info
43	Legg JW, et al. (2002) A novel PKC-regulated mechanism controls CD44 ezrin association and directional cell motility. Nat Cell Biol 4, 399-407 12032545 Curated Info
44	Lewis CA, Townsend PA, Isacke CM (2001) Ca(2+)/calmodulin-dependent protein kinase mediates the phosphorylation of CD44 required for cell migration on hyaluronan. Biochem J 357, 843-50 11463356 Curated Info
45	Peck D, Isacke CM (1998) Hyaluronan-dependent cell migration can be blocked by a CD44 cytoplasmic domain peptide containing a phosphoserine at position 325. J Cell Sci 111 ( Pt 11), 1595-601 9580567 Curated Info
46	Neame SJ, Isacke CM (1992) Phosphorylation of CD44 in vivo requires both Ser323 and Ser325, but does not regulate membrane localization or cytoskeletal interaction in epithelial cells. EMBO J 11, 4733-8 1281449 Curated Info

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