|Calculated MW||146808 Da|
|Other Names||Receptor tyrosine-protein kinase erbB-4, Proto-oncogene-like protein c-ErbB-4, Tyrosine kinase-type cell surface receptor HER4, p180erbB4, ERBB4 intracellular domain, 4ICD, E4ICD, s80HER4, ERBB4, HER4|
|Target/Specificity||A phospho-specific peptide corresponding to residues surrounding Tyrosine 1056 in human HER4/ErbB4 was used as an immunogen.|
|Format||50 mM Tris-Glycine (pH 7.4), 0.15 M NaCl, 40% Glycerol, 0.01% sodium azide and 0.05% BSA.|
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.|
|Precautions||Her4 Antibody Phospho (pY1056) is for research use only and not for use in diagnostic or therapeutic procedures.|
|Function||Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.|
|Cellular Location||Cell membrane; Single-pass type I membrane protein. Note=In response to NRG1 treatment, the activated receptor is internalized|
|Tissue Location||Expressed at highest levels in brain, heart, kidney, in addition to skeletal muscle, parathyroid, cerebellum, pituitary, spleen, testis and breast. Lower levels in thymus, lung, salivary gland, and pancreas. Isoform JM-A CYT-1 and isoform JM-B CYT-1 are expressed in cerebellum, but only the isoform JM-B is expressed in the heart.|
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HER4 / ErbB4 is a receptor tyrosine kinase that belongs to the human epidermal growth factor receptor (EGFR) family. ErbB4/HER4 is most predominantly expressed in several breast carcinoma cell lines, and in normal skeletal muscle, heart, pituitary, brain, and cerebellum (1). ErbB4/HER4 is activated by neuregulins (NRG), betacellulin (BTC), and heparin-binding EGF-like growth factor (2). Neuregulins regulate the expression of ligand- and voltage-gated channels in neurons and skeletal muscle by the activation of ErbB 1-4. The erbB4/HER4 receptor is unique among these receptors because its C-terminal tail binds to a protein motif known as the PDZ domain (3).
1. Plowman, G.D., et al. Proc Natl Acad Sci U S A. 90: 1746 2. Elenius, K., et al. J Biol Chem. 272: 26761 3. Garcia, R.A., et al. Proc Natl Acad Sci U S A. 97: 3596
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