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ERBB Signaling

The ERBB family of receptor tyrosine kinases (RTKs) plays a crucial role in cell growth, differentiation, and survival. It consists of four members: ERBB1 (EGFR), ERBB2 (HER2), ERBB3 (HER3), and ERBB4 (HER4). Epidermal growth factor (EGF) and other related growth factors bind to the extracellular domains of ERBB receptors, primarily EGFR (ERBB1). ERBB2 has no known direct ligand and relies on heterodimerization with other ERBB receptors. ERBB3 can bind heregulin but has impaired kinase activity. Dimerization: Upon ligand binding, ERBB receptors undergo conformational changes that promote their dimerization (homodimerization or heterodimerization). Heterodimerization, particularly with ERBB2, often leads to enhanced and prolonged signaling. ERBB2 is a preferred dimerization partner due to its constitutively active kinase domain and lack of direct ligand binding. It acts as a co-receptor, enhancing the signaling of other ERBB receptors. The phosphorylated tyrosine residues serve as docking sites for various signaling proteins containing Src homology 2 (SH2) domains. These proteins include adapter molecules and enzymes. Recruitment of these proteins activates several downstream signaling pathways, including activation of Ras, followed by Raf, MEK, and ERK, which leads to gene expression involved in cell proliferation and survival. Activation of PI3K, followed by Akt and mTOR, promotes cell growth, survival, and protein synthesis. STAT proteins are recruited to the receptors, phosphorylated, and then translocate to the nucleus to regulate gene transcription. PLCγ Pathway: Phospholipase C-gamma activation leads to the production of diacylglycerol and inositol triphosphate, affecting calcium signaling and protein kinase C activation. Dysregulation of ERBB signaling, such as overexpression, amplification, or mutations of ERBB receptors (particularly EGFR and HER2), is frequently observed in various cancers. This leads to uncontrolled cell proliferation, survival, and metastasis. The importance of ERBB signaling in cancer has led to the development of targeted therapies, such as tyrosine kinase inhibitors (TKIs) that block the kinase activity of ERBB receptors, and monoclonal antibodies that target the extracellular domains of these receptors. Overall, ERBB signaling is a complex and finely tuned network essential for normal cellular processes. Its dysregulation contributes significantly to disease, making it a critical area of research and therapeutic intervention, especially in oncology.

Human ERBB Signaling Primer Library
A ready-to-use Human ERBB Signaling PCR primer library that may be used to set up to 100 PCR arrays. Contains 88 primer sets directed against ERBB signaling genes and 8 housekeeping gene primer sets.

Provided in a 96-well microplate (20 ul - 10 uM)

Perform up to 100 PCR arrays (based on 20 ul assay volume per reaction)

Just add cDNA template and SYBR green master mix



GENE LIST:



ABL1 ABL proto-oncogene 1, non-receptor tyrosine kinase

AKT1 v-akt murine thymoma viral oncogene homolog 1

AKT2 v-akt murine thymoma viral oncogene homolog 2

AKT3 v-akt murine thymoma viral oncogene homolog 3

ARAF A-Raf proto-oncogene, serine/threonine kinase

AREG amphiregulin

BAD BCL2-associated agonist of cell death

BCL2 B-cell CLL/lymphoma 2

BCL2L11 BCL2-like 11 (apoptosis facilitator)

BIRC5 baculoviral IAP repeat containing 5

BRAF B-Raf proto-oncogene, serine/threonine kinase

BTC betacellulin

CAMK2A calcium/calmodulin-dependent protein kinase II alpha

CAMK2B calcium/calmodulin-dependent protein kinase II beta

CAMK2D calcium/calmodulin-dependent protein kinase II delta

CAMK2G calcium/calmodulin-dependent protein kinase II gamma

CBL Cbl proto-oncogene, E3 ubiquitin protein ligase

CBLB Cbl proto-oncogene B, E3 ubiquitin protein ligase

CCND1 cyclin D1

CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1)

CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1)

CRK v-crk avian sarcoma virus CT10 oncogene homolog

CRKL v-crk avian sarcoma virus CT10 oncogene homolog-like

E2F2 E2F transcription factor 2

EGF epidermal growth factor

EGFR epidermal growth factor receptor

EIF4EBP1 eukaryotic translation initiation factor 4E binding protein 1

ELK1 ELK1, member of ETS oncogene family

ERBB2 erb-b2 receptor tyrosine kinase 2

ERBB3 erb-b2 receptor tyrosine kinase 3

ERBB4 erb-b2 receptor tyrosine kinase 4

EREG epiregulin

FOXA1 forkhead box A1

FOXO1 forkhead box O1

GAB1 GRB2-associated binding protein 1

GRB2 growth factor receptor-bound protein 2

GSK3A glycogen synthase kinase 3 alpha

GSK3B glycogen synthase kinase 3 beta

HIF1A hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)

HRAS Harvey rat sarcoma viral oncogene homolog

IGF1R insulin-like growth factor 1 receptor

JUN jun proto-oncogene

KRAS Kirsten rat sarcoma viral oncogene homolog

MAP2K1 mitogen-activated protein kinase kinase 1

MAP2K2 mitogen-activated protein kinase kinase 2

MAP2K4 mitogen-activated protein kinase kinase 4

MAP2K7 mitogen-activated protein kinase kinase 7

MAPK10 mitogen-activated protein kinase 10

MAPK8 mitogen-activated protein kinase 8

MAPK9 mitogen-activated protein kinase 9

MDM2 MDM2 proto-oncogene, E3 ubiquitin protein ligase

MTOR mechanistic target of rapamycin (serine/threonine kinase)

MYC V-mycmyelocytomatosis viral oncogene homolog (avian)

NCK1 NCK adaptor protein 1

NCK2 NCK adaptor protein 2

NRAS neuroblastoma RAS viral (v-ras) oncogene homolog

NRG1 neuregulin 1

NRG2 neuregulin 2

NRG3 neuregulin 3

NRG4 neuregulin 4

PAK1 p21 protein (Cdc42/Rac)-activated kinase 1

PAK2 p21 protein (Cdc42/Rac)-activated kinase 2

PAK3 p21 protein (Cdc42/Rac)-activated kinase 3

PAK4 p21 protein (Cdc42/Rac)-activated kinase 4

PAK6 p21 protein (Cdc42/Rac)-activated kinase 6

PDK1 pyruvate dehydrogenase kinase, isozyme 1

PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha

PIK3CB phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta

PLCG1 phospholipase C, gamma 1

PLCG2 phospholipase C, gamma 2 (phosphatidylinositol-specific)

PRKCA protein kinase C, alpha

PRKCB protein kinase C, beta

PRKCG protein kinase C, gamma

PTEN phosphatase and tensin homolog

PTK2 protein tyrosine kinase 2

PTPN21 protein tyrosine phosphatase, non-receptor type 21

RAF1 Raf-1 proto-oncogene, serine/threonine kinase

RPS6KB1 ribosomal protein S6 kinase, 70kDa, polypeptide 1

RPS6KB2 ribosomal protein S6 kinase, 70kDa, polypeptide 2

SHC1 SHC (Src homology 2 domain containing) transforming protein 1

SHC2 SHC (Src homology 2 domain containing) transforming protein 2

SOS1 son of sevenless homolog 1

SOS2 son of sevenless homolog 2

SRC SRC proto-oncogene, non-receptor tyrosine kinase

STAT5A signal transducer and activator of transcription 5A

STAT5B signal transducer and activator of transcription 5B

TGFA transforming growth factor, alpha

TP53 tumor protein p53

ACTB Actin, beta

B2M Beta-2-microglobulin

GAPDH Glyceraldehyde-3-phosphate dehydrogenase

GUSB Glucuronidase, beta

HPRT1 Hypoxanthine phosphoribosyltransferase 1

PGK1 Phosphoglycerate kinase 1

PPIA Peptidylprolyl isomerase A

RPL13A Ribosomal protein L13a
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HERBB-I