HER4 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases (RTK).  Four members of the EGFR family have been identified: EGFR (ERBB1, HER1), HER2 (ERBB2), HER3 (ERBB3) and HER4 (ERBB4).  They typically contain an extracellular ligand binding domain (ECD), a transmembrane domain (TM), and an intracellular kinase domain that can interact with a multitude of signaling molecules and exhibit both ligand-dependent and ligand-independent activity.  EGFR signaling is initiated by ligand binding to the extracellular ligand binding domain. This initiates receptor homo-/hetero-dimerization and autophosphorylation by the intracellular kinase domain, resulting in receptor activation. Following activation, phosphorylation of cytoplasmic substrates occurs and a signaling cascade is initiated that drives many cellular responses, including changes in gene expression, cytoskeletal rearrangement, anti-apoptosis and increased cell proliferation.  HER4 ligands include the neuregulins (NRGs), β-cellulin and heparin-binding EGF-like growth factor (HB-EGF). The ligand binding induces a variety of cellular responses including mitogenesis and differentiation.  Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. HER4 and its ligand NRG1 are also implicated in the pathophysiology of schizophrenia.

HER4 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases (RTK).  Four members of the EGFR family have been identified: EGFR (ERBB1, HER1), HER2 (ERBB2), HER3 (ERBB3) and HER4 (ERBB4).  They typically contain an extracellular ligand binding domain (ECD), a transmembrane domain (TM), and an intracellular kinase domain that can interact with a multitude of signaling molecules and exhibit both ligand-dependent and ligand-independent activity.  EGFR signaling is initiated by ligand binding to the extracellular ligand binding domain. This initiates receptor homo-/hetero-dimerization and autophosphorylation by the intracellular kinase domain, resulting in receptor activation. Following activation, phosphorylation of cytoplasmic substrates occurs and a signaling cascade is initiated that drives many cellular responses, including changes in gene expression, cytoskeletal rearrangement, anti-apoptosis and increased cell proliferation.  HER4 ligands include the neuregulins (NRGs), β-cellulin and heparin-binding EGF-like growth factor (HB-EGF). The ligand binding induces a variety of cellular responses including mitogenesis and differentiation.  Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. HER4 and its ligand NRG1 are also implicated in the pathophysiology of schizophrenia.

 

Product Details

 

Gene Symbol: HER4; ERBB4; HER-4; p180erbB4; p180-erbB4

 

NCBI Gene ID: 2066 (human)

 

Uniprot Entry: Q15303 (human)

 

Construct Details: Full length human HER4 gene is subcloned into the Lentiviral expression vector pLTC with an upstream CMV promoter, which can be used for both transient and stable expression in mammalian cells.  It is co-transfected with the LentiPAK DNA mix (SKU# LP-001) into HEK293 cells to produce high titer lentiviral particles.

 

Vector Type: pLTC (lentiviral expression vector containing a heterologous CMV promoter, see the vector map above)

 

Formulation: Lentivector encoded and pre-packaged viral particles in the conditional medium (serum-free) from HEK293 cells that have been transfected with the lentivector gene clone and the LentiPAK DNA mix (average titer 10⁶ - 10⁷ IFU/ml)

 

Gene Insert Size: 3927 (bp)

 

Gene Insert Sequence:  

ATGAAGCCGGCGACAGGACTTTGGGTCTGGGTGAGCCTTCTCGTGGCGGCGGGGACCGTCCAGCCCAGCGATTCTCAGTC 

AGTGTGTGCAGGAACGGAGAATAAACTGAGCTCTCTCTCTGACCTGGAACAGCAGTACCGAGCCTTGCGCAAGTACTATG

AAAACTGTGAGGTTGTCATGGGCAACCTGGAGATAACCAGCATTGAGCACAACCGGGACCTCTCCTTCCTGCGGTCTGTT

CGAGAAGTCACAGGCTACGTGTTAGTGGCTCTTAATCAGTTTCGTTACCTGCCTCTGGAGAATTTACGCATTATTCGTGG

GACAAAACTTTATGAGGATCGATATGCCTTGGCAATATTTTTAAACTACAGAAAAGATGGAAACTTTGGACTTCAAGAAC

TTGGATTAAAGAACTTGACAGAAATCCTAAATGGTGGAGTCTATGTAGACCAGAACAAATTCCTTTGTTATGCAGACACC

ATTCATTGGCAAGATATTGTTCGGAACCCATGGCCTTCCAACTTGACTCTTGTGTCAACAAATGGTAGTTCAGGATGTGG

ACGTTGCCATAAGTCCTGTACTGGCCGTTGCTGGGGACCCACAGAAAATCATTGCCAGACTTTGACAAGGACGGTGTGTG

CAGAACAATGTGACGGCAGATGCTACGGACCTTACGTCAGTGACTGCTGCCATCGAGAATGTGCTGGAGGCTGCTCAGGA

CCTAAGGACACAGACTGCTTTGCCTGCATGAATTTCAATGACAGTGGAGCATGTGTTACTCAGTGTCCCCAAACCTTTGT

CTACAATCCAACCACCTTTCAACTGGAGCACAATTTCAATGCAAAGTACACATATGGAGCATTCTGTGTCAAGAAATGTC

CACATAACTTTGTGGTAGATTCCAGTTCTTGTGTGCGTGCCTGCCCTAGTTCCAAGATGGAAGTAGAAGAAAATGGGATT

AAAATGTGTAAACCTTGCACTGACATTTGCCCAAAAGCTTGTGATGGCATTGGCACAGGATCATTGATGTCAGCTCAGAC

TGTGGATTCCAGTAACATTGACAAATTCATAAACTGTACCAAGATCAATGGGAATTTGATCTTTCTAGTCACTGGTATTC

ATGGGGACCCTTACAATGCAATTGAAGCCATAGACCCAGAGAAACTGAACGTCTTTCGGACAGTCAGAGAGATAACAGGT

TTCCTGAACATACAGTCATGGCCACCAAACATGACTGACTTCAGTGTTTTTTCTAACCTGGTGACCATTGGTGGAAGAGT

ACTCTATAGTGGCCTGTCCTTGCTTATCCTCAAGCAACAGGGCATCACCTCTCTACAGTTCCAGTCCCTGAAGGAAATCA

GCGCAGGAAACATCTATATTACTGACAACAGCAACCTGTGTTATTATCATACCATTAACTGGACAACACTCTTCAGCACA

ATCAACCAGAGAATAGTAATCCGGGACAACAGAAAAGCTGAAAATTGTACTGCTGAAGGAATGGTGTGCAACCATCTGTG

TTCCAGTGATGGCTGTTGGGGACCTGGGCCAGACCAATGTCTGTCGTGTCGCCGCTTCAGTAGAGGAAGGATCTGCATAG

AGTCTTGTAACCTCTATGATGGTGAATTTCGGGAGTTTGAGAATGGCTCCATCTGTGTGGAGTGTGACCCCCAGTGTGAG

AAGATGGAAGATGGCCTCCTCACATGCCATGGACCGGGTCCTGACAACTGTACAAAGTGCTCTCATTTTAAAGATGGCCC

AAACTGTGTGGAAAAATGTCCAGATGGCTTACAGGGGGCAAACAGTTTCATTTTCAAGTATGCTGATCCAGATCGGGAGT 

GCCACCCATGCCATCCAAACTGCACCCAAGGGTGTAACGGTCCCACTAGTCATGACTGCATTTACTACCCATGGACGGGC

CATTCCACTTTACCACAACATGCTAGAACTCCCCTGATTGCAGCTGGAGTAATTGGTGGGCTCTTCATTCTGGTCATTGT

GGGTCTGACATTTGCTGTTTATGTTAGAAGGAAGAGCATCAAAAAGAAAAGAGCCTTGAGAAGATTCTTGGAAACAGAGT

TGGTGGAACCATTAACTCCCAGTGGCACAGCACCCAATCAAGCTCAACTTCGTATTTTGAAAGAAACTGAGCTGAAGAGG

GTAAAAGTCCTTGGCTCAGGTGCTTTTGGAACGGTTTATAAAGGTATTTGGGTACCTGAAGGAGAAACTGTGAAGATTCC

TGTGGCTATTAAGATTCTTAATGAGACAACTGGTCCCAAGGCAAATGTGGAGTTCATGGATGAAGCTCTGATCATGGCAA 

GTATGGATCATCCACACCTAGTCCGGTTGCTGGGTGTGTGTCTGAGCCCAACCATCCAGCTGGTTACTCAACTTATGCCC

CATGGCTGCCTGTTGGAGTATGTCCACGAGCACAAGGATAACATTGGATCACAACTGCTGCTTAACTGGTGTGTCCAGAT

AGCTAAGGGAATGATGTACCTGGAAGAAAGACGACTCGTTCATCGGGATTTGGCAGCCCGTAATGTCTTAGTGAAATCTC

CAAACCATGTGAAAATCACAGATTTTGGGCTAGCCAGACTCTTGGAAGGAGATGAAAAAGAGTACAATGCTGATGGAGGA

AAGATGCCAATTAAATGGATGGCTCTGGAGTGTATACATTACAGGAAATTCACCCATCAGAGTGACGTTTGGAGCTATGG 

AGTTACTATATGGGAACTGATGACCTTTGGAGGAAAACCCTATGATGGAATTCCAACGCGAGAAATCCCTGATTTATTAG

AGAAAGGAGAACGTTTGCCTCAGCCTCCCATCTGCACTATTGACGTTTACATGGTCATGGTCAAATGTTGGATGATTGAT 

GCTGACAGTAGACCTAAATTTAAGGAACTGGCTGCTGAGTTTTCAAGGATGGCTCGAGACCCTCAAAGATACCTAGTTAT 

TCAGGGTGATGATCGTATGAAGCTTCCCAGTCCAAATGACAGCAAGTTCTTTCAGAATCTCTTGGATGAAGAGGATTTGG 

AAGATATGATGGATGCTGAGGAGTACTTGGTCCCTCAGGCTTTCAACATCCCACCTCCCATCTATACTTCCAGAGCAAGA

ATTGACTCGAATAGGAGTGAAATTGGACACAGCCCTCCTCCTGCCTACACCCCCATGTCAGGAAACCAGTTTGTATACCG 

AGATGGAGGTTTTGCTGCTGAACAAGGAGTGTCTGTGCCCTACAGAGCCCCAACTAGCACAATTCCAGAAGCTCCTGTGG

CACAGGGTGCTACTGCTGAGATTTTTGATGACTCCTGCTGTAATGGCACCCTACGCAAGCCAGTGGCACCCCATGTCCAA

GAGGACAGTAGCACCCAGAGGTACAGTGCTGACCCCACCGTGTTTGCCCCAGAACGGAGCCCACGAGGAGAGCTGGATGA

GGAAGGTTACATGACTCCTATGCGAGACAAACCCAAACAAGAATACCTGAATCCAGTGGAGGAGAACCCTTTTGTTTCTC

GGAGAAAAAATGGAGACCTTCAAGCATTGGATAATCCCGAATATCACAATGCATCCAATGGTCCACCCAAGGCCGAGGAT

GAGTATGTGAATGAGCCACTGTACCTCAACACCTTTGCCAACACCTTGGGAAAAGCTGAGTACCTGAAGAACAACATACT

GTCAATGCCAGAGAAGGCCAAGAAAGCGTTTGACAACCCTGACTACTGGAACCACAGCCTGCCACCTCGGAGCACCCTTC

AGCACCCAGACTACCTGCAGGAGTACAGCACAAAATATTTTTATAAACAGAATGGGCGGATCCGGCCTATTGTGGCAGAG

AATCCTGAATACCTCTCTGAGTTCTCCCTGAAGCCAGGCACTGTGCTGCCGCCTCCACCTTACAGACACCGGAATACTGT

GGTGTAA

 

Primers: Gene insert coding sequence can be confirmed by following primers:

(a) forward (or 5'-end) primer: 5’-CAAATGGGCGGTAGGCGTG-3’;

(b) reverse (or 3'-end) primer: 5’-CGGGAAGCAATAGCATGATA-3’

 

 

Note: The sequence may vary due to the naturally occurring variants or mutations, such as single nucleotide polymorphism, or the artifact during PCR amplification.  High fidelity PCR systems should always be used. 

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

Important Safety Information: With the safety features in place, our lentiviral vectors and viral particles can be employed in standard Biosafety Level 2 tissue culture facilities and should be treated with the same level of caution as any other potentially infectious agent. Any investigator who purchases our lentiviral/retroviral products & services is responsible for following Biosafety Level 2 requirements on the handling of viral particles. For more information on Biosafety Level 2 agents and practices, please refer to NIH’s “Biosafety Considerations for Research with Lentiviral Vectors”.

Restriction: This product is not transferable or re-sellable.  Customer obtain no right to transfer, assign, or sublicense its use rights, or to transfer, resell, package, or otherwise distribute the product, or to use the product for the benefit of any third party or for any commercial purpose.  Customer may only use the product in compliance with applicable local, state and federal laws, regulations and rules.  Customer may not directly or indirectly use the product or allow the transfer, transmission, export or re-export of all or any part of the product in violation of any export control law or regulation of the united states or any other relevant jurisdiction.  Your use of this product constitutes acceptance of the terms of this limited use agreement.  Please refer to our “terms & conditions” for details.  If you are not willing to accept the limitation of this agreement, G&P Biosciences will accept return of the product for a full/partial refund.

 

Storage

 

The product is shipped at 4°C for immediate use.  Upon receipt, centrifuge the vial briefly before opening.  Store at –80°C or lower and the product is stable for 3 months.  Avoid repeated freeze-thaw cycles.

 

 

The product should be employed in a Biosafety Level 2 tissue culture facility. 

 

 

 

 

FOR RESEARCH USE ONLY. NOT FOR USE IN HUMAN. NOT RESELLABLE OR TRANSFERABLE

 

Your use of this product constitutes acceptance of the Terms & Conditions from G&P Biosciences.

 

 

References

 

1. Cancer Research 48:4083, 1988

2. Nature 378: 390-394, 1995

3. Nature Genet. 41: 1127-1132, 2009

4. Nature Med. 12: 824-828, 2006

 

 

Documentation

 

Product datasheet (pdf) can be downloaded here. LTV0157-PDS.pdf

 

 

 

Additional supporting documents, including COA and MSDS are available upon request.

 

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

 

Restriction: This product is not transferable or re-sellable.  Customer obtain no right to transfer, assign, or sublicense its use rights, or to transfer, resell, package, or otherwise distribute the product, or to use the product for the benefit of any third party or for any commercial purpose.  Customer may only use the product in compliance with applicable local, state and federal laws, regulations and rules.  Customer may not directly or indirectly use the product or allow the transfer, transmission, export or re-export of all or any part of the product in violation of any export control law or regulation of the united states or any other relevant jurisdiction.  Your use of this product constitutes acceptance of the terms of this limited use agreement.  Please refer to our “terms & conditions” for details.  If you are not willing to accept the limitation of this agreement, G&P Biosciences will accept return of the product for a full/partial refund.