Product: Phospho-IGF1 Receptor (Tyr1161) Antibody
Catalog: AF4397
Description: Rabbit polyclonal antibody to Phospho-IGF1 Receptor (Tyr1161)
Application: WB
Reactivity: Human, Mouse, Rat, Pig
Prediction: Bovine, Rabbit, Dog, Chicken, Xenopus
Mol.Wt.: 96kDa; 155kD(Calculated).
Uniprot: P08069
RRID: AB_2844462

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Product Info

Source:
Rabbit
Application:
WB 1:500-1:2000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human,Mouse,Rat,Pig
Prediction:
Bovine(100%), Rabbit(100%), Dog(100%), Chicken(100%), Xenopus(100%)
Clonality:
Polyclonal
Specificity:
Phospho-IGF1 Receptor (Tyr1161) Antibody detects endogenous levels of IGF1 Receptor only when phosphorylated at Tyr1161.
RRID:
AB_2844462
Cite Format: Affinity Biosciences Cat# AF4397, RRID:AB_2844462.
Conjugate:
Unconjugated.
Purification:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
Storage:
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.
Alias:

Fold/Unfold

CD221; CD221 antigen; IGF 1 receptor; IGF 1R; IGF I receptor; IGF-I receptor; Igf1r; IGF1R_HUMAN; IGFIR; IGFIRC; IGFR; Insulin like growth factor 1 receptor; Insulin like growth factor 1 receptor precursor; Insulin-like growth factor 1 receptor beta chain; Insulin-like growth factor I receptor; JTK13; MGC142170; MGC142172; MGC18216; Soluble IGF1R variant 1; Soluble IGF1R variant 2;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Expression:
P08069 IGF1R_HUMAN:

Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Overexpressed in tumors, including melanomas, cancers of the colon, pancreas prostate and kidney.

Sequence:
MKSGSGGGSPTSLWGLLFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLENCTVIEGYLHILLISKAEDYRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGWKLFYNYALVIFEMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTVDWSLILDAVSNNYIVGNKPPKECGDLCPGTMEEKPMCEKTTINNEYNYRCWTTNRCQKMCPSTCGKRACTENNECCHPECLGSCSAPDNDTACVACRHYYYAGVCVPACPPNTYRFEGWRCVDRDFCANILSAESSDSEGFVIHDGECMQECPSGFIRNGSQSMYCIPCEGPCPKVCEEEKKTKTIDSVTSAQMLQGCTIFKGNLLINIRRGNNIASELENFMGLIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLEGNYSFYVLDNQNLQQLWDWDHRNLTIKAGKMYFAFNPKLCVSEIYRMEEVTGTKGRQSKGDINTRNNGERASCESDVLHFTSTTTSKNRIIITWHRYRPPDYRDLISFTVYYKEAPFKNVTEYDGQDACGSNSWNMVDVDLPPNKDVEPGILLHGLKPWTQYAVYVKAVTLTMVENDHIRGAKSEILYIRTNASVPSIPLDVLSASNSSSQLIVKWNPPSLPNGNLSYYIVRWQRQPQDGYLYRHNYCSKDKIPIRKYADGTIDIEEVTENPKTEVCGGEKGPCCACPKTEAEKQAEKEEAEYRKVFENFLHNSIFVPRPERKRRDVMQVANTTMSSRSRNTTAADTYNITDPEELETEYPFFESRVDNKERTVISNLRPFTLYRIDIHSCNHEAEKLGCSASNFVFARTMPAEGADDIPGPVTWEPRPENSIFLKWPEPENPNGLILMYEIKYGSQVEDQRECVSRQEYRKYGGAKLNRLNPGNYTARIQATSLSGNGSWTDPVFFYVQAKTGYENFIHLIIALPVAVLLIVGGLVIMLYVFHRKRNNSRLGNGVLYASVNPEYFSAADVYVPDEWEVAREKITMSRELGQGSFGMVYEGVAKGVVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIMELMTRGDLKSYLRSLRPEMENNPVLAPPSLSKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIISSIKEEMEPGFREVSFYYSEENKLPEPEELDLEPENMESVPLDPSASSSSLPLPDRHSGHKAENGPGPGVLVLRASFDERQPYAHMNGGRKNERALPLPQSSTC

Predictions

Predictions:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

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

PTMs - P08069 As Substrate

Site PTM Type Enzyme
S9 Phosphorylation
N51 N-Glycosylation
Y113 Phosphorylation
Y115 Phosphorylation
T123 Phosphorylation
Y131 Phosphorylation
N135 N-Glycosylation
N244 N-Glycosylation
N314 N-Glycosylation
T468 Phosphorylation
R471 Methylation
S473 Phosphorylation
R480 Methylation
S623 Phosphorylation
S624 Phosphorylation
K672 Ubiquitination
Y973 Phosphorylation P12931 (SRC) , P08069 (IGF1R)
Y980 Phosphorylation P08069 (IGF1R) , P12931 (SRC)
S982 Phosphorylation P08069 (IGF1R)
S1009 Phosphorylation
Y1014 Phosphorylation
K1033 Ubiquitination
K1055 Sumoylation
K1088 Acetylation
K1130 Sumoylation
K1150 Sumoylation
Y1161 Phosphorylation P12931 (SRC) , P08069 (IGF1R)
T1163 Phosphorylation
Y1165 Phosphorylation P12931 (SRC) , P08069 (IGF1R)
Y1166 Phosphorylation P08069 (IGF1R) , P12931 (SRC)
K1168 Ubiquitination
K1171 Ubiquitination
S1193 Phosphorylation
S1278 Phosphorylation P25098 (GRK2)
Y1280 Phosphorylation P08069 (IGF1R)
Y1281 Phosphorylation P08069 (IGF1R)
S1308 Phosphorylation
S1310 Phosphorylation
S1311 Phosphorylation
S1312 Phosphorylation
S1313 Phosphorylation
S1321 Phosphorylation P43250 (GRK6)
S1339 Phosphorylation
Y1346 Phosphorylation P08069 (IGF1R)
K1354 Methylation
S1364 Phosphorylation
T1366 Phosphorylation
C1367 S-Nitrosylation

PTMs - P08069 As Enzyme

Substrate Site Source
O15530 (PDPK1) Y373 Uniprot
O15530 (PDPK1) Y376 Uniprot
P07550 (ADRB2) Y132 Uniprot
P07550 (ADRB2) Y141 Uniprot
P08069 (IGF1R) Y973 Uniprot
P08069 (IGF1R) Y980 Uniprot
P08069 (IGF1R) S982 Uniprot
P08069 (IGF1R) Y1161 Uniprot
P08069 (IGF1R) Y1165 Uniprot
P08069 (IGF1R) Y1166 Uniprot
P08069 (IGF1R) Y1280 Uniprot
P08069 (IGF1R) Y1281 Uniprot
P08069 (IGF1R) Y1346 Uniprot
P35568 (IRS1) Y465 Uniprot
P35568 (IRS1) Y612 Uniprot
P35568 (IRS1) Y632 Uniprot
P35568 (IRS1) Y662 Uniprot
P35568 (IRS1) Y732 Uniprot
P35568 (IRS1) Y896 Uniprot
P35568 (IRS1) Y941 Uniprot
P35568 (IRS1) Y989 Uniprot
P35568 (IRS1) Y1179 Uniprot
P35568 (IRS1) Y1229 Uniprot
P46108 (CRK) Y221 Uniprot
P78324 (SIRPA) Y470 Uniprot
P78324 (SIRPA) Y496 Uniprot

Research Backgrounds

Function:

Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.

When present in a hybrid receptor with INSR, binds IGF1.shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast,shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.

PTMs:

Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner; Tyr-1165 is predominantly phosphorylated first, followed by phosphorylation of Tyr-1161 and Tyr-1166. While every single phosphorylation increases kinase activity, all three tyrosine residues in the kinase activation loop (Tyr-1165, Tyr-1161 and Tyr-1166) have to be phosphorylated for optimal activity. Can be autophosphorylated at additional tyrosine residues (in vitro). Autophosphorylated is followed by phosphorylation of juxtamembrane tyrosines and C-terminal serines. Phosphorylation of Tyr-980 is required for IRS1- and SHC1-binding. Phosphorylation of Ser-1278 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1282. Dephosphorylated by PTPN1 (By similarity).

Polyubiquitinated at Lys-1168 and Lys-1171 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome. Ubiquitination is facilitated by pre-existing phosphorylation.

Sumoylated with SUMO1.

Controlled by regulated intramembrane proteolysis (RIP). Undergoes metalloprotease-dependent constitutive ectodomain shedding to produce a membrane-anchored 52 kDa C-Terminal fragment which is further processed by presenilin gamma-secretase to yield an intracellular 50 kDa fragment.

Subcellular Location:

Cell membrane>Single-pass type I membrane protein.

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

Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Overexpressed in tumors, including melanomas, cancers of the colon, pancreas prostate and kidney.

Subunit Structure:

Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chain carries the kinase domain. Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. Forms a hybrid receptor with INSR, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with RACK1. Interacts with SOCS1, SOCS2 and SOCS3. Interacts with 14-3-3 proteins. Interacts with NMD2. Interacts with MAP3K5. Interacts with STAT3. Found in a ternary complex with IGF1 and ITGAV:ITGB3 or ITGA6:ITGB4. Interacts (nascent precursor form) with ZFAND2B.

Family&Domains:

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Research Fields

· Cellular Processes > Cell growth and death > Oocyte meiosis.   (View pathway)

· Cellular Processes > Transport and catabolism > Autophagy - animal.   (View pathway)

· Cellular Processes > Transport and catabolism > Endocytosis.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Focal adhesion.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Adherens junction.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Signaling pathways regulating pluripotency of stem cells.   (View pathway)

· Environmental Information Processing > Signal transduction > MAPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Ras signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Rap1 signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > HIF-1 signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > FoxO signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > mTOR signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > PI3K-Akt signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > AMPK signaling pathway.   (View pathway)

· Human Diseases > Drug resistance: Antineoplastic > EGFR tyrosine kinase inhibitor resistance.

· Human Diseases > Drug resistance: Antineoplastic > Endocrine resistance.

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

· Human Diseases > Cancers: Overview > Transcriptional misregulation in cancer.

· Human Diseases > Cancers: Overview > Proteoglycans in cancer.

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

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

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

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

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

· Organismal Systems > Aging > Longevity regulating pathway.   (View pathway)

· Organismal Systems > Aging > Longevity regulating pathway - multiple species.   (View pathway)

· Organismal Systems > Nervous system > Long-term depression.

· Organismal Systems > Endocrine system > Ovarian steroidogenesis.

· Organismal Systems > Endocrine system > Progesterone-mediated oocyte maturation.

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