Phospho-DDR1 (Tyr513) Antibody [F16D7]

Application: Reactivity: Human

Usage Information

Dilution
WB1:1000

Application
WB

Reactivity
Human

Source
Rabbit Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW
125 kDa

Datasheet & SDS

Biological Description

Specificity
Phospho-DDR1 (Tyr513) Antibody [F16D7] detects endogenous levels of total DDR1 protein only when it is phosphorylated at Tyr513.

Clone
F16D7

Synonym(s)
CAK, CD167, CD167 antigen-like family member A, CD167a, Cell adhesion kinase, DDR, DDR1, HGK2, mammarian carcinoma kinase 10, Mammary carcinoma kinase 10, MCK-10, MCK10, NEP, neuroepithelial tyrosine kinase, PTK3, PTK3A, RTK6, TRK E, TRKE

Background
Phospho-DDR1 (Tyr513) represents the activated state of discoidin domain receptor 1, a non-canonical receptor tyrosine kinase within the DDR family that is distinguished by its unique activation by extracellular matrix collagens rather than soluble growth factors, positioning it as a critical sensor of tissue stiffness and matrix composition in epithelial and stromal cells. The DDR1 protein contains an extracellular discoidin domain that binds diverse collagens including type I, II, III, IV, V, and VI, a single transmembrane helix, and an intracellular kinase domain with an activation loop where Tyr513 resides, serving as a key autophosphorylation site that correlates with kinase activity and downstream signaling propagation. Collagen binding induces DDR1 clustering into dense membrane aggregates, which drives trans-autophosphorylation at Tyr513 and other tyrosine residues independent of classical kinase activation conformations, and this clustering mechanism positions Tyr513 phosphorylation as a direct readout of receptor engagement with fibrillar collagen matrices. Phosphorylation at Tyr513 creates docking sites for SH2 domain-containing proteins, including Src family kinases, Shp-2 phosphatase, and adaptor proteins such as Shc and Grb2, which recruit downstream effectors and initiate PI3K, MAPK, and Akt signaling cascades that control cell adhesion, migration, proliferation, and survival. DDR1-mediated signaling through the Tyr513 phospho-epitope upregulates matrix metalloproteinase expression, drives collagen remodeling, and modulates epithelial-mesenchymal transition, thereby integrating matrix sensing with proteolytic activity and cytoskeletal reorganization during tissue morphogenesis and repair. DDR1 Tyr513 phosphorylation is inhibited by selective small-molecule inhibitors with nanomolar potency, including DDR1-IN-5 and DDR1-IN-6, which suppress autophosphorylation and block downstream oncogenic signaling, establishing this site as a pharmacologically tractable marker of DDR1 activation in cancer and fibrotic disease models. Pathological conditions involving aberrant collagen deposition and matrix remodeling, including breast carcinoma, pulmonary fibrosis, liver fibrosis, and cardiovascular disease, display elevated DDR1 Tyr513 phosphorylation, linking this modification to disease progression through enhanced cell-matrix adhesion, invasive migration, and sustained proliferative signaling in tumor microenvironments and fibrotic tissues. DDR1 expression is restricted to epithelial lineages in normal tissues, particularly in the kidney, lung, gastrointestinal tract, and brain, and its dysregulation leads to altered tissue architecture, impaired branching morphogenesis in mammary gland development, and aberrant immune responses that affect tumor immunity and chronic inflammation.

Background

Phospho-DDR1 (Tyr513) represents the activated state of discoidin domain receptor 1, a non-canonical receptor tyrosine kinase within the DDR family that is distinguished by its unique activation by extracellular matrix collagens rather than soluble growth factors, positioning it as a critical sensor of tissue stiffness and matrix composition in epithelial and stromal cells. The DDR1 protein contains an extracellular discoidin domain that binds diverse collagens including type I, II, III, IV, V, and VI, a single transmembrane helix, and an intracellular kinase domain with an activation loop where Tyr513 resides, serving as a key autophosphorylation site that correlates with kinase activity and downstream signaling propagation. Collagen binding induces DDR1 clustering into dense membrane aggregates, which drives trans-autophosphorylation at Tyr513 and other tyrosine residues independent of classical kinase activation conformations, and this clustering mechanism positions Tyr513 phosphorylation as a direct readout of receptor engagement with fibrillar collagen matrices. Phosphorylation at Tyr513 creates docking sites for SH2 domain-containing proteins, including Src family kinases, Shp-2 phosphatase, and adaptor proteins such as Shc and Grb2, which recruit downstream effectors and initiate PI3K, MAPK, and Akt signaling cascades that control cell adhesion, migration, proliferation, and survival. DDR1-mediated signaling through the Tyr513 phospho-epitope upregulates matrix metalloproteinase expression, drives collagen remodeling, and modulates epithelial-mesenchymal transition, thereby integrating matrix sensing with proteolytic activity and cytoskeletal reorganization during tissue morphogenesis and repair. DDR1 Tyr513 phosphorylation is inhibited by selective small-molecule inhibitors with nanomolar potency, including DDR1-IN-5 and DDR1-IN-6, which suppress autophosphorylation and block downstream oncogenic signaling, establishing this site as a pharmacologically tractable marker of DDR1 activation in cancer and fibrotic disease models. Pathological conditions involving aberrant collagen deposition and matrix remodeling, including breast carcinoma, pulmonary fibrosis, liver fibrosis, and cardiovascular disease, display elevated DDR1 Tyr513 phosphorylation, linking this modification to disease progression through enhanced cell-matrix adhesion, invasive migration, and sustained proliferative signaling in tumor microenvironments and fibrotic tissues. DDR1 expression is restricted to epithelial lineages in normal tissues, particularly in the kidney, lung, gastrointestinal tract, and brain, and its dysregulation leads to altered tissue architecture, impaired branching morphogenesis in mammary gland development, and aberrant immune responses that affect tumor immunity and chronic inflammation.

References
https://pubmed.ncbi.nlm.nih.gov/36454444/ https://pubmed.ncbi.nlm.nih.gov/29467865/

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

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Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%