Growth factors and cytokines represent two classes of cell-signaling protein molecules that can confer positive and negative (inhibitory) effects on cell growth and proliferation. Both molecules types are secreted by numerous different cells and display a matching cell surface receptor, thus facilitating the alteration of cellular functions upon formation of intracellular signal cascades responsible for up- and down regulating individual genes and their associated transcription factors. Distinct changes in growth factor and cytokine levels have been linked to various disease states and conditions, thus modern research has focused on understanding disease onset and progression by investigating these cell-signaling molecules on a cellular level.
With research in mind, Rockland provides an exquisite panel of purified proteins and antibodies developed against these signaling molecules for use in the analyses by western blot, ELISA, Immunohistochemistry, FLISA and many more.
EGF displays a very high affinity for binding to its cellular surface epidermal growth factor receptor (EGFR); thereby stimulating the intrinsic protein-tyrosine kinase activity of the receptor. In turn, activity of the tyrosine kinase translates into a signal transduction cascade resulting in a variety of biochemical changes within the cell including elevated intracellular calcium levels, increased glycolysis and protein synthesis. Furthermore, upregulation of gene expression levels including the EGF gene result in increased DNA synthesis followed by cell proliferation. EGF proliferates growth of mesodermal and ectodermal cells, while inhibiting growth of certain carcinomas and decreasing gastric acid secretion.
Platelet-Derived Growth Factor (PDGF) represents one of the many secreted growth factors responsible for regulating growth and division. It is a dimeric glycoprotein consisting of two distinct polypeptide chains – either homodimeric A/A or B/B chain arrangements or a heterodimeric combination of the two (AB). As described for EGF, PGDF binds to its specific cell surface receptor referred to as the PDGF receptor or PDGFR. This receptor displays intrinsic tyrosine kinase activity and upon auto-phosphorylation of the PDGF receptor results in the binding of cofactors responsible for intitating numerous signal transduction cascades affecting downstream regulation of gene expression and the cell cycle.
Five different PDGF isoforms classified as ligands A (PDGFA), B (PDGFB), C (PDGFC), and D (PDGFD) and the AB heterodimer are capable of binding to two distict hetero- or homo- dimeric receptor isoforms, PDGFR alpha and PDGFR beta, with varying affinity. Proliferative responses to PDGF are exerted on many mesenchymal cell types, with other growth-related responses to PDGF including cytoskeletal rearrangement and increased polyphosphoinositol turnover.
FGFs are heparin-binding proteins; their interaction with cell surface associated heparan sulfate proteoglycans has proven essential for FGF induced signal transduction. These multifunctional growth factors are essential in the proliferation and differentiation of a wide variety of cells types and tissues and are primarily associated with angiogenesis, wound healing and embryonic development.
Structurally related, the family of human FGFs includes 22 members displaying differing functionalities. FGFs play a dominant role in the development of the skeletal system and nervous system in mammals and are also neurotrophic for cells of both the peripheral and central nervous system.
Cytokines are a unique class of secreted signaling proteins produced by a variety of hematopoietic and non-hematopoietic cell types. These are extensively used in cellular communication regulating immune functions and embryogenesis. Cell surface receptors are specific to individual cytokines that upon occupation induce intracellular signaling cascades resulting in the alteration of cellular functions. These may include the upregulation and/or downregulation of genes and their associated transcription factors; result in the synthesis of other cytokines; increase in the number of cell surface receptors for other molecules or suppress their own effect by feedback inhibition. They can exert autocrine, paracrine and endocrine effects and are secreted primarily from leukocytes. Cytokines stimulate the humoral and cellular immune responses, as well as the activation of phagocytic cells.
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Common applications for Rockland growth factors and cytokines include:
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