Growth Factors

Epidermal growth factor (EGF) family members play a critical role in cell proliferation, differentiation, and survival. Other than EGF, the first identified family member, the family contains HB-EGF, TGF-α, amphiregulin, epiregulin, epigen, betacellulin and neuregulins. All of the family members contain 6 cysteine residues which form 3 disulfide bonds generating a structural loop required for binding EGF receptors (EGFRs). EGFRs are receptor tyrosine kinases that, when activated, dimerize and initiate downstream MAPK, AKT, and JNK signaling pathways. EGF and EGFRs can be found upregulated in a number of different cancer types.

LEGENDplex™ Human Growth Factor Panel

Fibroblast growth factor (FGF) family members play key roles in signaling during development, regulating diverse pathways such as proliferation, survival, migration, differentiation and organogenesis. In adults, FGF signaling is induced in injury and plays a role in wound healing. Expressed in almost all tissues, the FGF family includes 23 members which bind to four distinct tyrosine kinase receptors designated FGFR1-4 and function in downstream signaling pathways including RAS-MAPK, PI3K-AKT, PLCγ, and STAT. In addition, there are non-signaling FGF molecules which regulate intracellular voltage gated sodium channels.

LEGENDplex™ Human Growth Factor Panel

Human PBMCs (1x106 cells/mL) were cultured under various conditions (PHA, 10 μg/mL; PMA, 50 ng/mL; Control, no treatment). Supernatants were collected after 4 days then assayed with the LEGENDplex™ Human Growth Factor Panel (Cat. No. 740180).

The Hedgehog protein family regulates early development and stem cell maintenance and differentiation. In adult tissues, they are important in tissue remodeling and aberrant regulation of this pathway is associated with carcinogenesis. In vertebrates, the Hedgehog family contains sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog (DHH). Hedgehog proteins are cleaved to yield an N-terminal fragment which is important for signaling and a C-terminal fragment which is glycosylated and is active in precursor processing. The C-terminal domain mediates the covalent attachment of a cholesterol moiety to the N-terminal restricting it to the cell surface. In conjunction with the Hedgehog interaction protein (HIP), hedgehog proteins bind to the Patched receptor, which associates with the Smoothened receptor, to activate transcription of target genes.

The insulin-growth factors (IGF) family contains three members (IGF-I, IGF-II, and IGF-III) and shares a structural similarity with insulin. IGFs act as a hormone and are important during growth and development and have anabolic effects in adult tissues. The IGF family binds to one of two IGF tyrosine kinase receptors, and this signaling cascade regulates proliferation, survival, differentiation, and migration. There are seven IGF binding proteins (IGFBP) which serve to both regulate the availability of IGF family members and extend the half-life of the IGF peptides. Additionally, as the binding proteins bind to the IGFs with different affinities they also regulate interactions with the IGF receptors and can modulate their actions.

LEGENDplex™ Human IGFBP Panel

Normal human serum samples from 10 different donors were tested for endogenous levels of human IGFBP proteins using the LEGENDplex™ Human IGFBP Panel (Cat. No. 740468).

Neurotrophin growth factors regulate the development, growth, and survival of neurons specifically in regulating injury induced neuron regeneration, differentiation of neuronal populations in the peripheral and central nervous system, axonal growth, and modulating dendritic growth and morphology. These growth factors share a tertiary-folded structure containing a cysteine-knot domain. Though neurotrophins function in a specific cell type, the signaling mechanism is similar to other growth factor families as they bind tyrosine kinase receptors which autophosphorylate initiating a phosphorylation cascade. Dysregulation of neurotrophins is related to neurological disorders such as Alzheimer's disease.

LEGEND MAX™ Mouse LIF ELISA kit

Lungs were harvested from a mouse and dissected into small pieces (~1 mm3) and cultured in 10% FBS/RPMI. Supernatants were removed at 1, 2, 3, and 7 days and LIF concentrations were quantified using the LEGEND MAX™ Mouse LIF ELISA Kit (Cat. No. 445107).

The platelet-derived growth factor (PDGF) family is defined by 5 different isotypes consisting of dilsulfide-linked homo- or hetero-dimers of four poly peptides known as the A, B, C, and D chains. Like the VEGF family, PDGFs contain a cysteine-knot domain. PDGF-A and –B chains must undergo intracellular activation while PDGF-C and –D are secreted before being processed by extracellular proteases. PDGFs are mitogenic, function to direct cell migration, and are typically found in neural or mesenchymal cells. Additionally, PDGFs are synthesized, stored, and released by platelets upon activation. PDGF receptors are dimeric receptors consisting of two tyrosine-kinase receptor subunits and upon surface binding signal through a phosphorylation cascade.

Certain growth factors, sometimes referred to as hematopoietic growth factors, regulate the proliferation and survival of stem cells as well as influence differentiation of hematopoietic stem cells to various lineages. These growth factors are often found in the bone marrow niche and can be produced by fibroblasts, endothelial cells, and mature lymphocytes, monocytes and macrophages. As these cytokines directly influence differentiation into particular cell types, recombinant growth factors have been used in clinical settings. For example, exogenously administered EPO can stimulate erythropoiesis and is used to help treat anemias. Other stem cell growth factors such as G-CSF and GM-CSF are often used during bone marrow transplantation to stimulate the donor pool of peripheral blood progenitors.

LEGENDplex™ Mouse HSC Panel

Head tissue from E10.5 mouse embryos (n = 6) was digested and then sorted using FACS to isolate endothelial cells (CD31posCD41negCD45neg). Cells were then cultured with OP9-DL1 cells, a bone-marrow derived stromal cell line that ectopically expresses the Notch ligand, Delta-like 1 (DL1). This in vitro culture system allows for the commitment, differentiation, and proliferation of T cells from hemogenic endothelial cells. Cells were co-cultured for 7 days, and then supernatants were assayed using the LEGENDplex™ Mouse HSC panel (Cat. No. 740676). Data courtesy of Dr. Zhuan Li, MRC Centre for Inflammation Research at the University of Edinburgh.

The transforming growth factor (TGF) superfamily contains over 30 proteins, including TGFβs, BMPs and activins. The TGF family members, particularly the earliest member TGF-β, have been well-studied for their role in immunoregulation including roles in inflammation and response to infection. Additionally, TGFs play an important role in development and tissue homeostasis. TGF family members typically exist as either homo- or heterodimers and are proteolytically cleaved prior to activation and subsequent receptor binding. TGFs bind to what is designated as type I and type II receptor complexes. TGF receptors typically signal through SMAD proteins to regulate transcription of target genes in the nucleus; however, TGF family members can also activate p38, JNK, ERK-MAPK, and PI3K-AKT signaling pathways. As TGFs regulate the immune system and proliferation/growth pathways, they can both suppress and support tumor growth, depending on the cell context.

LEGENDplex™ Human Free Active/Total TGF-β1 Assay

Human serum samples were tested for free active or Total TGF-β1 using the LEGENDplex™ Human Free Active/Total TGF-β1 Panel (Cat. No. 740449).

The Tumor necrosis factor (TNF) superfamily is one of the largest growth factor families as it consists of approximately 19 ligands which bind to approximately 29 receptors. The TNF family plays important roles in regulating the immune response and hematopoiesis. While many TNF family members are membrane-bound ligands which act locally, they can also be shed from the membrane and the soluble ligands can act as either agonists or antagonists. Once bound to a TNF receptor, TNF growth factors mediate apoptosis, particularly those ligands which bind receptors containing a death domain, or regulate proliferation by activating pathways such as the NF-κB, JNK, or MAPK signaling pathways. Like most pathways involved in apoptosis and proliferation, alterations with the TNF superfamily are associated with a number of disease states including tumorigenesis and autoimmune diseases.

PE anti-human CD357 (GITR) Antibody

Human peripheral blood lymphocytes were activated for 3 days with PHA, and then stained with CD3 Alexa Fluor® 647 and CD357 (GITR) (clone 108-17) PE (top) or mouse IgG2a, κ PE isotype control (bottom).

Vascular endothelial growth factors (VEGFs) are widely expressed mitogens, particularly important in vascular endothelial cells where they play a critical role in regulating angiogenesis and permeability of capillary blood vessels. Cytokines, hypoxia, and oncogenes can all induce VEGF expression. Like PDGF family members, they contain eight cysteine residues which form what is known as a cysteine-knot structure. There are five main members of the VEGF family: VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PGF). Additionally, VEGF-A (commonly referred to as VEGF) can be alternatively spliced to produce a number of different isoforms. In general, VEGF family members bind to receptor tyrosine kinases (VEGFRs) on the cell surface where the receptors dimerize and become activated through transphosphorylation. VEGF can also bind to neuropilins on neurons where they stimulate angiogenesis.

LEGENDplex™ Human Growth Factor Panel

Human PBMCs (1x106 cells/mL) were cultured under various conditions (PHA, 10 μg/mL; PMA, 50 ng/mL; Control, no treatment). Supernatants were collected after 4 days then assayed with the LEGENDplex™ Human Growth Factor Panel (Cat. No. 740180).

Other growth factors do not fall under a specific family name but like all growth factors, they typically exist in a soluble form and bind to transmembrane receptors initiating downstream signaling cascades. Other than influencing proliferation, differentiation and immune responses, these growth factors have specific functions in certain cell types. For example, prolactin is best known for its role in enabling lactation and asprosin regulates metabolic pathways and promotes glucose release in hepatocytes.