Tyr1062
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Home > Phosphorylation Site Page: > Tyr1062  -  Ret (human)

Site Information
TWIENkLyGMsDPNW   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447625

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 32 ) , [32P] bio-synthetic labeling ( 32 , 33 ) , immunoprecipitation ( 22 , 30 ) , mass spectrometry ( 2 , 6 , 12 ) , microscopy-colocalization with upstream kinase ( 20 ) , mutation of modification site ( 4 , 7 , 8 , 10 , 11 , 14 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 29 , 30 , 31 , 32 , 33 ) , phospho-antibody ( 3 , 5 , 7 , 9 , 10 , 11 , 13 , 15 , 18 , 20 , 21 , 22 , 24 , 25 , 28 , 29 , 30 , 31 ) , phosphopeptide mapping ( 33 ) , western blotting ( 3 , 5 , 7 , 9 , 10 , 11 , 13 , 18 , 20 , 21 , 24 , 30 , 31 )
Disease tissue studied:
adrenal cancer ( 4 , 20 , 21 ) , pheochromocytoma ( 4 , 20 , 21 ) , breast cancer ( 5 , 12 ) , breast adenocarcinoma ( 12 ) , neuroblastoma ( 2 , 6 , 24 ) , thyroid cancer ( 10 , 11 , 13 ) , medullary thyroid carcinoma ( 10 )
Relevant cell line - cell type - tissue:
'neuron, superior cervical ganglion'-brain ( 27 ) , 'neuron, superior cervical ganglion'-brain [Ret (mouse), homozygous knockout] ( 8 ) , 'neuron, sympathetic' ( 4 ) , 293 (epithelial) ( 3 , 7 , 10 , 11 , 18 , 26 ) , 3T3 (fibroblast) [Ret (human)] ( 32 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 25 ) , 3T3 (fibroblast) ( 10 , 18 , 23 , 27 , 31 ) , ARO (thyroid cell) ( 28 ) , CHP126 (neural crest) ( 15 ) , COS (fibroblast) ( 4 , 14 , 20 , 21 , 24 , 33 ) , DU4475 (breast cell) ( 12 ) , HEK293T (epithelial) ( 13 ) , LAN-6 (neural crest) ( 2 , 6 ) , MCF-7 (breast cell) ( 5 ) , MG87 (fibroblast) ( 24 , 27 ) , MN1 (neuron) ( 24 ) , Neuro-2a (neuron) ( 15 , 24 ) , neuron-dorsal root ganglia ( 24 ) , PC CL 3 (thyroid cell) ( 17 , 19 ) , PC-12 (chromaffin) ( 4 , 20 , 21 , 30 ) , SH-SY5Y (neural crest) ( 22 ) , SK-N-MC (neural crest) ( 25 , 29 ) , SKNSH (neural crest) ( 25 ) , TGW (neuron) ( 25 , 29 ) , thyroid ( 10 , 20 ) , TPC-1 (thyroid cell) ( 11 , 13 , 28 ) , TT (thyroid cell) ( 28 )

Upstream Regulation
Regulatory protein:
Ret (human) ( 3 , 10 , 20 )
Putative in vivo kinases:
Ret (human) ( 32 )
Kinases, in vitro:
Ret (human) ( 16 , 24 , 33 ) , Ret (mouse) ( 32 )
Putative upstream phosphatases:
PTPRJ (human) ( 13 )
Phosphatases, in vitro:
PTPRJ (human) ( 13 )
Treatments:
ART ( 24 ) , GDNF ( 5 , 9 , 10 , 15 , 22 , 24 , 25 , 27 , 29 ) , imatinib ( 3 , 10 ) , neurturin ( 24 ) , NVP-TAE226 ( 3 ) , PP1 ( 3 ) , PP2 ( 10 ) , sorafenib ( 3 )

Downstream Regulation
Effects of modification on Ret:
enzymatic activity, induced ( 22 , 25 , 26 ) , molecular association, regulation ( 4 , 11 , 14 , 15 , 18 , 21 , 25 , 26 , 27 , 29 , 30 , 32 ) , phosphorylation ( 11 , 27 )
Effects of modification on biological processes:
apoptosis, induced ( 19 ) , apoptosis, inhibited ( 30 ) , cell growth, altered ( 4 , 20 , 23 , 24 , 28 , 31 ) , cytoskeletal reorganization ( 22 ) , transcription, altered ( 17 )
Induce interaction with:
CRK (human) ( 11 ) , DOK6 (human) ( 15 ) , FRS2 (human) ( 25 ) , GAB1 (human) ( 11 ) , IRS1 (human) ( 26 ) , PIK3R1 (human) ( 27 ) , PIK3R1 (rat) ( 30 ) , PKCA (human) ( 18 ) , RAPGEF1 (human) ( 11 ) , SHC1 (human) ( 14 , 25 , 26 , 27 , 29 ) , SHC3 (human) ( 21 ) , SHP-2 (human) ( 4 )

References 

1

Plaza-Menacho I, et al. (2016) RET Functions as a Dual-Specificity Kinase that Requires Allosteric Inputs from Juxtamembrane Elements. Cell Rep 17, 3319-3332
28009299   Curated Info

2

Palacios-Moreno J, et al. (2015) Neuroblastoma Tyrosine Kinase Signaling Networks Involve FYN and LYN in Endosomes and Lipid Rafts. PLoS Comput Biol 11, e1004130
25884760   Curated Info

3

Plaza-Menacho I, et al. (2011) Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET-FAK transactivation mechanism. J Biol Chem 286, 17292-302
21454698   Curated Info

4

Perrinjaquet M, Vilar M, Ibáñez CF (2010) Protein-tyrosine phosphatase SHP2 contributes to GDNF neurotrophic activity through direct binding to phospho-Tyr687 in the RET receptor tyrosine kinase. J Biol Chem 285, 31867-75
20682772   Curated Info

5

Plaza-Menacho I, et al. (2010) Targeting the receptor tyrosine kinase RET sensitizes breast cancer cells to tamoxifen treatment and reveals a role for RET in endocrine resistance. Oncogene 29, 4648-57
20531297   Curated Info

6

Guo A (2009) CST Curation Set: 6121; Year: 2009; Biosample/Treatment: cell line, LAN-6/NGF; Disease: neuroblastoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

7

Lodyga M, et al. (2009) XB130, a tissue-specific adaptor protein that couples the RET/PTC oncogenic kinase to PI 3-kinase pathway. Oncogene 28, 937-49
19060924   Curated Info

8

Encinas M, et al. (2008) Analysis of Ret knockin mice reveals a critical role for IKKs, but not PI 3-K, in neurotrophic factor-induced survival of sympathetic neurons. Cell Death Differ 15, 1510-21
18497757   Curated Info

9

Runeberg-Roos P, Virtanen H, Saarma M (2007) RET(MEN 2B) is active in the endoplasmic reticulum before reaching the cell surface. Oncogene 26, 7909-15
17599050   Curated Info

10

Plaza-Menacho I, et al. (2007) Ras/ERK1/2-mediated STAT3 Ser727 phosphorylation by familial medullary thyroid carcinoma-associated RET mutants induces full activation of STAT3 and is required for c-fos promoter activation, cell mitogenicity, and transformation. J Biol Chem 282, 6415-24
17209045   Curated Info

11

De Falco V, et al. (2007) RET/papillary thyroid carcinoma oncogenic signaling through the Rap1 small GTPase. Cancer Res 67, 381-90
17210721   Curated Info

12

Michaud C (2006) CST Curation Set: 1814; Year: 2006; Biosample/Treatment: cell line, DU4475/serum starved; Disease: breast adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

13

Iervolino A, et al. (2006) The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins. Cancer Res 66, 6280-7
16778204   Curated Info

14

Scott RP, Eketjäll S, Aineskog H, Ibáñez CF (2005) Distinct turnover of alternatively spliced isoforms of the RET kinase receptor mediated by differential recruitment of the Cbl ubiquitin ligase. J Biol Chem 280, 13442-9
15677445   Curated Info

15

Crowder RJ, et al. (2004) Dok-6, a Novel p62 Dok family member, promotes Ret-mediated neurite outgrowth. J Biol Chem 279, 42072-81
15286081   Curated Info

16

Kawamoto Y, et al. (2004) Identification of RET autophosphorylation sites by mass spectrometry. J Biol Chem 279, 14213-24
14711813   Curated Info

17

Castellone MD, et al. (2004) Autocrine stimulation by osteopontin plays a pivotal role in the expression of the mitogenic and invasive phenotype of RET/PTC-transformed thyroid cells. Oncogene 23, 2188-96
14981541   Curated Info

18

Andreozzi F, et al. (2003) Protein kinase Calpha activation by RET: evidence for a negative feedback mechanism controlling RET tyrosine kinase. Oncogene 22, 2942-9
12771945   Curated Info

19

Castellone MD, et al. (2003) Ras-mediated apoptosis of PC CL 3 rat thyroid cells induced by RET/PTC oncogenes. Oncogene 22, 246-55
12527893   Curated Info

20

Buckwalter TL, et al. (2002) The roles of phosphotyrosines-294, -404, and -451 in RET/PTC1-induced thyroid tumor formation. Oncogene 21, 8166-72
12444552   Curated Info

21

Pelicci G, et al. (2002) The neuron-specific Rai (ShcC) adaptor protein inhibits apoptosis by coupling Ret to the phosphatidylinositol 3-kinase/Akt signaling pathway. Mol Cell Biol 22, 7351-63
12242309   Curated Info

22

Fukuda T, Kiuchi K, Takahashi M (2002) Novel mechanism of regulation of Rac activity and lamellipodia formation by RET tyrosine kinase. J Biol Chem 277, 19114-21
11886862   Curated Info

23

Kato M, et al. (2002) Repair by Src kinase of function-impaired RET with multiple endocrine neoplasia type 2A mutation with substitutions of tyrosines in the COOH-terminal kinase domain for phenylalanine. Cancer Res 62, 2414-22
11956105   Curated Info

24

Coulpier M, Anders J, Ibáñez CF (2002) Coordinated activation of autophosphorylation sites in the RET receptor tyrosine kinase: importance of tyrosine 1062 for GDNF mediated neuronal differentiation and survival. J Biol Chem 277, 1991-9
11713247   Curated Info

25

Kurokawa K, et al. (2001) Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction. Oncogene 20, 1929-38
11360177   Curated Info

26

Melillo RM, et al. (2001) The insulin receptor substrate (IRS)-1 recruits phosphatidylinositol 3-kinase to Ret: evidence for a competition between Shc and IRS-1 for the binding to Ret. Oncogene 20, 209-18
11313948   Curated Info

27

Besset V, Scott RP, Ibáñez CF (2000) Signaling complexes and protein-protein interactions involved in the activation of the Ras and phosphatidylinositol 3-kinase pathways by the c-Ret receptor tyrosine kinase. J Biol Chem 275, 39159-66
10995764   Curated Info

28

Salvatore D, et al. (2000) Tyrosines 1015 and 1062 are in vivo autophosphorylation sites in ret and ret-derived oncoproteins. J Clin Endocrinol Metab 85, 3898-907
11061555   Curated Info

29

Hayashi H, et al. (2000) Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell line-derived neurotrophic factor. Oncogene 19, 4469-75
11002419   Curated Info

30

De Vita G, et al. (2000) Tyrosine 1062 of RET-MEN2A mediates activation of Akt (protein kinase B) and mitogen-activated protein kinase pathways leading to PC12 cell survival. Cancer Res 60, 3727-31
10919641   Curated Info

31

Iwashita T, et al. (1999) Biological and biochemical properties of Ret with kinase domain mutations identified in multiple endocrine neoplasia type 2B and familial medullary thyroid carcinoma. Oncogene 18, 3919-22
10445857   Curated Info

32

Asai N, Murakami H, Iwashita T, Takahashi M (1996) A mutation at tyrosine 1062 in MEN2A-Ret and MEN2B-Ret impairs their transforming activity and association with shc adaptor proteins. J Biol Chem 271, 17644-9
8663426   Curated Info

33

Liu X, et al. (1996) Oncogenic RET receptors display different autophosphorylation sites and substrate binding specificities. J Biol Chem 271, 5309-12
8621380   Curated Info

34

Zhu H, et al. (1994) Tyrosine 1356 in the carboxyl-terminal tail of the HGF/SF receptor is essential for the transduction of signals for cell motility and morphogenesis. J Biol Chem 269, 29943-8
7961992   Curated Info