产品: 磷酸化 Ret (Tyr1062) 抗体
货号: AF3120
描述: Rabbit polyclonal antibody to Phospho-Ret (Tyr1062)
应用: WB IF/ICC
反应: Human, Mouse, Rat
预测: Pig, Zebrafish, Bovine, Sheep, Rabbit, Dog, Xenopus
分子量: 175kDa; 124kD(Calculated).
蛋白号: P07949
RRID: AB_2834555

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产品描述

来源:
Rabbit
应用:
WB 1:500-1:2000, IF/ICC 1:100-1:500
*The optimal dilutions should be determined by the end user.
*Tips:

WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.

反应:
Human,Mouse,Rat
预测:
Pig(100%), Zebrafish(100%), Bovine(100%), Sheep(100%), Rabbit(100%), Dog(100%), Xenopus(100%)
克隆:
Polyclonal
特异性:
Phospho-Ret (Tyr1062) Antibody detects endogenous levels of Ret only when phosphorylated at Tyrosine 1062.
RRID:
AB_2834555
引用格式: Affinity Biosciences Cat# AF3120, RRID:AB_2834555.
偶联:
Unconjugated.
纯化:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
别名:

展开/折叠

C ret; Cadherin family member 12; Cadherin related family member 16; CDHF 12; CDHF12; CDHR16; ELKS Fusion gene; HSCR 1; HSCR1; Hydroxyaryl protein kinase; MEN2A; MEN2B; MTC 1; MTC1; Multiple endocrine neoplasia and medullary thyroid carcinoma 1; Oncogene RET; Proto oncogene tyrosine protein kinase receptor ret; Proto-oncogene c-Ret; Proto-oncogene tyrosine-protein kinase receptor ret; PTC; RET; RET ELE1; Ret Proto oncogene; RET transforming sequence; RET_HUMAN; RET51; RET9; tyrosine-protein kinase receptor ret;

抗原和靶标

免疫原:
Uniprot:
基因/基因ID:
描述:
This gene, a member of the cadherin superfamily, encodes one of the receptor tyrosine kinases, which are cell-surface molecules that transduce signals for cell growth and differentiation. This gene plays a crucial role in neural crest development, and it can undergo oncogenic activation in vivo and in vitro by cytogenetic rearrangement.
序列:
MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQEDTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENRPPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAPTFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNRNLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCSTLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGRCEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLCDELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFPRKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKENASPSELRDLLSEFNVLKQVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRESRKVGPGYLGSGGSRNSSSLDHPDERALTMGDLISFAWQISQGMQYLAEMKLVHRDLAARNILVAEGRKMKISDFGLSRDVYEEDSYVKRSQGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERLFNLLKTGHRMERPDNCSEEMYRLMLQCWKQEPDKRPVFADISKDLEKMMVKRRDYLDLAASTPSDSLIYDDGLSEEETPLVDCNNAPLPRALPSTWIENKLYGMSDPNWPGESPVPLTRADGTNTGFPRYPNDSVYANWMLSPSAAKLMDTFDS

种属预测

种属预测:

score>80的预测可信度较高,可尝试用于WB检测。*预测模型主要基于免疫原序列比对,结果仅作参考,不作为质保凭据。

Species
Results
Score
Pig
100
Bovine
100
Sheep
100
Dog
100
Xenopus
100
Zebrafish
100
Rabbit
100
Horse
0
Chicken
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

翻译修饰 - P07949 作为底物

Site PTM Type Enzyme
N151 N-Glycosylation
S159 Phosphorylation
T350 Phosphorylation
T675 Phosphorylation P17252 (PRKCA)
S686 Phosphorylation
Y687 Phosphorylation P07949 (RET)
S688 Phosphorylation
S696 Phosphorylation P17612 (PRKACA)
S699 Phosphorylation
S705 Phosphorylation
Y752 Phosphorylation
T754 Phosphorylation
Y791 Phosphorylation
Y806 Phosphorylation P07949 (RET)
Y809 Phosphorylation P07949 (RET)
Y826 Phosphorylation P07949 (RET)
Y864 Phosphorylation
S891 Phosphorylation
Y900 Phosphorylation P07949 (RET)
S904 Phosphorylation
Y905 Phosphorylation Q05397 (PTK2) , P07949 (RET) , P12931 (SRC)
S909 Phosphorylation
Y928 Phosphorylation
Y952 Phosphorylation
Y981 Phosphorylation P07949 (RET)
Y1015 Phosphorylation P07949 (RET)
Y1029 Phosphorylation P07949 (RET)
K1060 Ubiquitination
Y1062 Phosphorylation P07949 (RET)
S1065 Phosphorylation
Y1090 Phosphorylation P07949 (RET)
Y1096 Phosphorylation P07949 (RET)
K1107 Ubiquitination
T1111 Phosphorylation
S1114 Phosphorylation

翻译修饰 - P07949 作为激酶

Substrate Site Source
O15530 (PDPK1) Y9 Uniprot
P07949-1 (RET) Y687 Uniprot
P07949 (RET) Y806 Uniprot
P07949 (RET) Y809 Uniprot
P07949 (RET) Y826 Uniprot
P07949-2 (RET) Y900 Uniprot
P07949-2 (RET) Y905 Uniprot
P07949-2 (RET) Y981 Uniprot
P07949-1 (RET) Y1015 Uniprot
P07949-2 (RET) Y1029 Uniprot
P07949 (RET) Y1062 Uniprot
P07949 (RET) Y1090 Uniprot
P07949 (RET) Y1096 Uniprot
P18848 (ATF4) T107 Uniprot
P18848 (ATF4) T114 Uniprot
P18848 (ATF4) T115 Uniprot
P18848 (ATF4) T119 Uniprot
P19174 (PLCG1) Y783 Uniprot
P27361 (MAPK3) Y204 Uniprot
P27986 (PIK3R1) Y203 Uniprot
P28482-1 (MAPK1) Y187 Uniprot
P31749 (AKT1) Y315 Uniprot
P35222 (CTNNB1) Y654 Uniprot
P45983 (MAPK8) Y185 Uniprot
P45984-2 (MAPK9) Y185 Uniprot
Q05397 (PTK2) Y576 Uniprot
Q05397 (PTK2) Y577 Uniprot
Q05397 (PTK2) Y861 Uniprot
Q05397 (PTK2) Y925 Uniprot
Q16539 (MAPK14) T180 Uniprot
Q16539 (MAPK14) Y182 Uniprot
Q658W2 (DKFZp666O0110) Y598 Uniprot
Q658W2 (DKFZp666O0110) Y599 Uniprot
Q8N4X5 (AFAP1L2) Y54 Uniprot
Q99704 (DOK1) Y398 Uniprot

研究背景

功能:

Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways. Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL.

翻译修饰:

Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation. Dephosphorylated by PTPRJ on Tyr-905, Tyr-1015 and Tyr-1062.

Proteolytically cleaved by caspase-3. The soluble RET kinase fragment is able to induce cell death. The extracellular cell-membrane anchored RET cadherin fragment accelerates cell adhesion in sympathetic neurons.

细胞定位:

Cell membrane>Single-pass type I membrane protein. Endosome membrane>Single-pass type I membrane protein.
Note: Predominantly located on the plasma membrane. In the presence of SORL1 and GFRA1, directed to endosomes.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
亚基结构:

Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5 (By similarity). The phosphorylated form interacts with PLCG1 and GRB7 (By similarity). Interacts (not phosphorylated) with PTK2/FAK1 (via FERM domain). Extracellular cell-membrane anchored RET cadherin fragments form complex in neurons with reduced trophic status, preferentially at the contact sites between somas. Interacts with AIP in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex. Binds to ARTN (By similarity). Interacts (inactive) with CBLC and CD2AP; dissociates upon activation by GDNF which increases CBLC:CD2AP interaction. Interacts (via the extracellular domain) with GFRAL (via the extracellular domain); the interaction mediates cellular signaling upon interaction of GFRAL with its ligand GDF15. Interaction with GFRAL requires previous GDF15-binding to GFRAL. Interacts with GFRA1; in the presence of SORL1, the GFRA1/RET complex is targeted to endosomes. Interacts with GDNF.

蛋白家族:

Belongs to the protein kinase superfamily. Tyr protein kinase family.

研究领域

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Thyroid cancer.   (View pathway)

· Human Diseases > Cancers: Overview > Central carbon metabolism in cancer.   (View pathway)

文献引用

1). Wang Y et al. Growth differentiation factor-15 overexpression promotes cell proliferation and predicts poor prognosis in cerebral lower-grade gliomas correlated with hypoxia and glycolysis signature. Life Sciences 2022 May 16; (PubMed: 35588865) [IF=6.1]

2). Yang Z et al. CCL2/CCR2 Axis Promotes the Progression of Salivary Adenoid Cystic Carcinoma via Recruiting and Reprogramming the Tumor-Associated Macrophages. Frontiers in Oncology 2019 Apr 9;9:231 (PubMed: 31024838) [IF=4.7]

Application: WB    Species: human    Sample: SACC-83 cells

FIGURE 5 | TAMs promoted the proliferation, migration, and invasion of SACC cells via the GDNF/p-RET pathway. The TAMs conditioned media (TAMs-CM) was used to stimulate the SACC-83 cells. The macrophages conditioned media (macrophages-CM) served as the control. The CCR2 antagonist (RS504393, 50 ng/mL),GDNF NAb (2µg/mL), and RET antagonist (PYP-1, 5µM) were used. (A–C) The expression of p-RET and RET in SACC-83 cells were evaluated by western blot.

3). Gao R et al. Recurrent non-severe hypoglycemia aggravates cognitive decline in diabetes and induces mitochondrial dysfunction in cultured astrocytes. Molecular and Cellular Endocrinology 2021 Apr 15;526:111192. (PubMed: 33545179) [IF=4.1]

Application: WB    Species: mice    Sample: cortex tissue

Fig. 3. Recurrent non-severe hypoglycemia (RH) inhibits brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) signaling in diabetic mice. (A) The expression of BDNF/tropomyosin (t)-receptor (r)-kinase (k) B (TrkB) signaling and GDNF/GDNF family receptor alpha-1 (GFRa1)/receptor tyrosine kinase (Ret) signaling in mice cerebral cortex, measured using western blotting. (B–G) Relative protein levels of BDNF, TrkB, p-TrkB, GDNF, GFRa1, Ret, and p-Ret (Tyr1062), as determined by ImageJ. *P < 0.05 vs. normal control (NC), **P < 0.01 vs. NC, #P < 0.05 vs. diabetes mellitus (DM), ##P < 0.05 vs. DM.

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