Recombinant Human Cripto Protein (His Tag)

Beta LifeScience SKU/CAT #: BLPSN-1430

Recombinant Human Cripto Protein (His Tag)

Beta LifeScience SKU/CAT #: BLPSN-1430
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Product Overview

Tag His
Host Species Human
Accession AAH22393.1
Background Cripto/TDGF1 is a member of the epidermal growth factor (EGF)- Cripto, Frl-1, and Cryptic (CFC) family. EGF-CFC family member proteins share a variant EGF-like motif, a conserved cysteine-rich domain, and a C-terminal hydrophobic region. Before gastrulation, Cripto is asymmetrically expressed in a proximal-distal gradient in the epiblast, and subsequently is expressed in the primitive streak and newly formed embryonic mesoderm. These proteins play key roles in intercellular signaling pathways during vertebrate embryogenesis. Mutations in Cripto/TDGF1 can cause autosomal visceral heterotaxy. Cripto/TDGF1 is involved in left-right asymmetric morphogenesis during organ development. Cripto signalling is essential for the conversion of a proximal-distal asymmetry into an orthogonal anterior-posterior axis. The mechanism of inhibitory effects of the Cripto includes both cancer cell apoptosis, activation of c-Jun-NH(2)-terminal kinase and p38 kinase signaling pathways and blocking of Akt phosphorylation. Thus, Cripto is a unique target, and Immunohistochemistry to Cripto could be of therapeutic value for human cancers.
Description A DNA sequence encoding the human TDGF1 (AAH22393.1) (Met 1-Thr 172) with a C-terminal His tag was expressed.
Source HEK293
Predicted N Terminal Leu 31
AA Sequence Met 1-Thr 172
Molecular Weight The secreted recombinant human TDGF1 comprises 153 a.a. with a predicted molecular mass of 17.4 kDa. As a result of glycosylation, the apparent molecular mass of rhTDGF1 is approximately 25-30 kDa in SDS-PAGE under reducing conditions.
Purity >95% as determined by SDS-PAGE
Endotoxin < 1.0 EU per μg of the protein as determined by the LAL method
Bioactivity Measured by its binding ability in a functional ELISA. Immobilized human TDGF1 at 2 ug/ml (100 ul/well) can bind human ALK4 with a linear range of 0.0068-0.16 ug/ml.
Formulation Lyophilized from sterile PBS, pH 7.4.
Stability The recombinant proteins are stable for up to 1 year from date of receipt at -70°C.
Usage For Research Use Only
Storage Store the protein under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function GPI-anchored cell membrane protein involved in Nodal signaling. Cell-associated TDGF1 acts as a Nodal coreceptor in cis. Shedding of TDGF1 by TMEM8A modulates Nodal signaling by allowing soluble TDGF1 to act as a Nodal coreceptor on other cells. Could play a role in the determination of the epiblastic cells that subsequently give rise to the mesoderm.
Subcellular Location Cell membrane; Lipid-anchor, GPI-anchor. Secreted.
Protein Families EGF-CFC (Cripto-1/FRL1/Cryptic) family
Database References
Tissue Specificity Preferentially expressed in gastric and colorectal carcinomas than in their normal counterparts. Expressed in breast and lung.

Gene Functions References

  1. Cripto-1 expression is increased by OCT4 overexpression, but decreased by shRNA-mediated OCT4 knockdown. OCT4 overexpression significantly activates Cripto-1 transcriptional activity. A 5'-upstream minimal promoter sequence in the gene-encoding Cripto-1 is significantly activated by OCT4 overexpression. PMID: 29223130
  2. Targeting the Cripto-1/TAK-1/NF-kappaB/Survivin pathway may be an effective approach to combat apoptosis resistance in cancer. PMID: 29807222
  3. Knockdown of Cripto-1 inhibits the proliferation, migration, invasion, and angiogenesis in prostate carcinoma cells. PMID: 29358554
  4. Results identified elevated CR-1 expression in esophageal squamous cell carcinoma (ESCC) specimens which correlated to poor prognosis of the patients. CR-1 high cells isolated from ESCC cells possess cancer stem-like cells (ECSLC) properties. PMID: 28431580
  5. These results highlight a functional role for CRIPTO and GRP78 in prostate cancer metastasis and suggest that targeting CRIPTO/GRP78 signaling may have significant therapeutic potential. PMID: 28394345
  6. PGAP6 plays a critical role in Nodal signaling modulation through CRIPTO shedding. PMID: 27881714
  7. Upregulation of cripto-1 is associated with prostate cancer. PMID: 28098905
  8. the miR-15b expression is negatively associated with the cripto-1 expression in glioma cells. miR-15b may subsequently impair growth and invasion of glioma cells through targeted regulation of cripto-1. PMID: 27082313
  9. These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management. PMID: 26654129
  10. serum CR-1 is a useful diagnostic and prognostic marker for nonsmall cell lung cancer patients. PMID: 26109366
  11. Cripto-1 overexpression contributes to aggressiveness and poor prognosis of hepatocellular carcinoma PMID: 26375669
  12. The main signaling pathways mediating Cripto-1 effects include Nodal-dependent (Smad2/3) and Nodal-independent (Src/p44/42/Akt) signaling transduction pathways PMID: 26327334
  13. Cripto-1 is a novel and dynamically regulated effector of stem cell functions in colorectal cancer. PMID: 26343543
  14. these findings suggest a novel molecular network, involving CRIPTO, AKT, and FGFR signaling, in favor of the emergence of mesenchymal-like cancer cells during the development of aggressive prostate tumors. PMID: 25596738
  15. Report lower gene expression of Cripto in endometriosis but difference not maintained at protein level. PMID: 25228630
  16. Treatment of U-87 MG cells with CR-1 leads to higher expression of drug efflux protein MDR-1 in the CR-1 positive subpopulation, indicating correlated induction of these two proteins. PMID: 25658584
  17. These findings clearly suggest that the downregulation of miR-15a-16 with Cripto amplification may be involved in the development of nonsmall cell lung cancer. PMID: 24500260
  18. Snail represses Cripto-1 gene by direct transcriptional interaction PMID: 25889638
  19. CR-1 expression in glioblastoma multiforme(GBM)tissue and blood; CR-1 plasma levels from GBM patients were elevated compared with normal; CR-1 concentrations higher than normal correlated with shorter overall survival; identified CR-1 in different areas of GBM tissue including perivascular tumor cells and endothelial cells PMID: 24521322
  20. the functional analysis of the main associated locus identified a causal variant in the 5'UTR of CRIPTO gene which is able to strongly modulate CRIPTO expression through an AP-1-mediate transcriptional regulation. PMID: 25629528
  21. Our findings suggest that high Cripto-1 expression might be involved in the development of bladder cancer and a potentially effective prognostic marker in bladder cancer patients PMID: 25326807
  22. Over expression of Cripto-1 was correlated with the occurrence, development, metastasis and malignant degree of lung adenocarcinoma. PMID: 25796148
  23. these findings identify the CRIPTO/GRP78 pathway as a developmentally conserved regulator of fetal and adult mammary stem cell behavior ex vivo, with implications for the stem-like cells found in many cancers. PMID: 24749068
  24. This study demonstrated CR-1 expression in the placental bed, its increased expression in creta placentas, and EVT cells as the main CR-1-producing cell type. PMID: 25165718
  25. Data suggest that the high expression of Cripto-1 (CR-1) may play an important role in the progression of non-small cell lung cancer (NSCLC), and CR-1 expression may offer a valuable marker for predicting the outcome of patients with NSCLC. PMID: 24870591
  26. Tumors from NSCLC patients with EGFR-activating mutations that were intrinsically resistant to EGFR-TKIs expressed higher levels of CRIPTO1 compared with tumors from patients that were sensitive to EGFR-TKIs. PMID: 24911146
  27. Cripto is overexpressed in colonic neoplasms and is related to cancer cell migration/invasion. PMID: 24379580
  28. The significance of cell surface CR-1 expression in human melanoma cells, was examined. PMID: 23574716
  29. Cross-talk between Cripto-1 and the Wnt/beta-catenin signaling pathway might play a role in mammary transformation leading to a more aggressive behavior of mammary cancer cells. PMID: 23022962
  30. Offer some insight into the transcriptional regulation of CR-1 gene expression and its critical role in the pathogenesis of human cancer. PMID: 23129342
  31. human testicular tumors showed upregulation of NODAL and CRIPTO that was proportional to invasiveness and to the number of malignant cells. PMID: 23034635
  32. Cripto/GRP78 modulates the TGF-beta pathway in development and oncogenesis [review] PMID: 22306319
  33. Cripto-1 may play a role during developmental EMT, and it may also be involved in the reprogramming of differentiated tumor cells into cancer stem cells through the induction of an EMT program. PMID: 22542493
  34. Cripto-1 plays a role in the malignant transformation of oral mucosa and is involved in the tumorigenesis and progression of oral squamous cell carcinoma by promoting the growth and migration of malignant cells. PMID: 21824804
  35. High CRIPTO-1 is associated with cutaneous melanoma. PMID: 21863025
  36. Disturbed expression of endometrial activin A, cripto , and follistatin suggests a dysfunction of the activin pathway in endometriosis/endometrioma. PMID: 21496809
  37. work firstly provides human genetic evidence of TDGF1 involved in the pathogenesis of ventricular septal defects PMID: 19853938
  38. expression of CR-1 may alter the physiochemical properties of the plasma membrane resulting in an enhancement of intercellular transfer of cellular signaling components which may account for the paracrine activity of CR-1. PMID: 21055389
  39. Results demonstrate that CR-1 expression is enriched in an undifferentiated, tumorigenic subpopulation and is regulated by key regulators of pluripotent stem cells. PMID: 20549704
  40. molecular model of activin receptor-like kinase 4/Cripto/Nodal complex built by homology modeling as well as docking tests aimed at identifying potential binding epitopes PMID: 20629020
  41. TDGF1 has a role in metachronous metastasis of colorectal cancer PMID: 20126975
  42. TDGF-1, which is significantly upregulated in APA and mediates aldosterone hypersecretion and deregulated growth in adrenocortical cells in vitro, may represent a key player in the development and pathophysiology of primary aldosteronism. PMID: 20385969
  43. Nodal and Cripto immunoreactivity increased dramatically in the transition from histologic Grade 1 to histologic Grades 2 and 3 endometrial carcinomas. PMID: 19874624
  44. Cripto has dual roles as a coreceptor as well as a coligand for Nodal and that this signaling interaction with Nodal is regulated by an unusual form of glycosylation. PMID: 12052855
  45. A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects. PMID: 12073012
  46. complexation with activin and type II activin receptors and role in blocking activin signaling PMID: 12682303
  47. CRIPTO signaling promotes cardiomyogenesis and redirects the neural fate of embryonic stem cells. PMID: 14581455
  48. Results suggest that cripto-1 overexpression might be associated with the progression towards a more aggressive phenotype in breast carcinoma, through the activation of both Akt and Smad-2 signalling pathways. PMID: 14584041
  49. The regulation of Netrin-1 expression is important in regulating Cripto-1-dependent invasion and migration of mammary epithelial cells. PMID: 16176936
  50. The plasma CR-1 might represent a novel biomarker for the detection of breast and colon carcinomas. A statistically significant increase in the levels of plasma CR-1 was found in patients with colon carcinoma and in patients with breast carcinoma. PMID: 16951234


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