Fibroblast growth factor 1 (FGF-1) also known as acidic fibroblast growth factor (aFGF), is a

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for ...

and

signaling protein In biology, cell signaling (cell signalling in British English) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in both prokaryotes and eukaryo ...

encoded by the ''FGF1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. It is synthesized as a 155 amino acid polypeptide, whose mature form is a non-

glycosylated Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...

17-18 kDa protein.

Fibroblast growth factor Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by the macrophages. They are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in ...

protein was first purified in 1975, but soon afterwards others using different conditions isolated acidic FGF, Heparin-binding growth factor-1, and Endothelial cell growth factor-1. Gene sequencing revealed that this group was actually the same growth factor and that FGF1 was a member of a family of FGF proteins. FGF-1 has no definitive signal sequence and thus is not secreted through classical pathways, but it does appear to form a disulfide linked dimer inside cells that associate with a complex of proteins at the cell membrane (including S100A13 and Syt1) which then help flip it through the membrane to the exterior of the cell. Once in the reducing conditions of the surrounding tissue, the dimer dissociates into

monomer A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization. Classification Chemis ...

ic FGF1 that can enter systemic circulation or be sequestered in tissues binding to

heparan sulfate proteoglycan Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs in a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular ma ...

s of the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

. FGF1 can then bind to and exert its effects via specific fibroblast growth factor receptor (FGFR) proteins which themselves constitute a family of closely related molecules. In addition to its extracellular activity, FGF1 can also function intracellularly. The protein has a

nuclear localization sequence A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines ...

(NLS) but the route that FGF1 takes to get to the nucleus is unclear and it appears that some sort of cell surface receptor binding is necessary, followed by its internalization and translocation to the nucleus whereupon it can interact with nuclear isoforms of FGFRs. This is different from FGF2 which also can activate nuclear FGFRs but has splicing variants of the protein that never leave the cell and go directly to the nucleus.

Function

FGF family members possess broad

mitogenic A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The cell cycle Mitogens ac ...

and cell survival activities, and are involved in a variety of biological processes, including

embryonic development In developmental biology, animal embryonic development, also known as animal embryogenesis, is the developmental stage of an animal embryo. Embryonic development starts with the fertilization of an egg cell (ovum) by a sperm, sperm cell (spermat ...

cell growth Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...

, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...

- and neuroectoderm-derived cells in vitro, thus is thought to be involved in

organogenesis Organogenesis is the phase of embryonic development that starts at the end of gastrulation and continues until birth. During organogenesis, the three germ layers formed from gastrulation (the ectoderm, endoderm, and mesoderm) form the internal org ...

. Three alternatively spliced variants encoding different isoforms have been described. FGF1 is multifunctional with many reported effects. For one example, in mice with diet-induced diabetes that is an experimental equivalent of type 2 diabetes in humans, a single injection of the FGF1 protein is enough to restore blood sugar levels to a healthy range for > 2 days.*

Interactions

FGF1 has been shown to interact with: *

CSNK2A2 Casein kinase II subunit alpha' is an enzyme that in humans is encoded by the ''CSNK2A2'' gene. Interactions CSNK2A2 has been shown to interact with over 160 different substrates. CSNK2A2 has been shown to interact with: * Activating transc ...

CSNK2B Casein kinase II subunit beta is a protein that in humans is encoded by the ''CSNK2B'' gene. It is a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcription, translation, and replication. The enzyme local ...

CSNK2A1 Casein kinase II subunit alpha is an enzyme that in humans is encoded by the ''CSNK2A1'' gene. Casein kinase II is a serine/threonine protein kinase that phosphorylates acidic proteins such as casein. The kinase exists as a tetramer and is co ...

* FIBP * FGFR1 *

FGFR2 Fibroblast growth factor receptor 2 (FGFR-2) also known as CD332 (cluster of differentiation 332) is a protein that in humans is encoded by the ''FGFR2'' gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor. FGFR-2 is ...

FGFR3 Fibroblast growth factor receptor 3 (FGFR-3) is a protein that in humans is encoded by the ''FGFR3'' gene. FGFR3 has also been designated as CD333 (cluster of differentiation 333). The gene, which is located on chromosome 4, location p16.3, is e ...

FGFR4 Fibroblast growth factor receptor 4 (FGFR-4) is a protein that in humans is encoded by the ''FGFR4'' gene. FGFR4 has also been designated as CD334 (cluster of differentiation 334). The protein encoded by this gene is a member of the fibroblast gr ...

HSPA9 Mitochondrial 70kDa heat shock protein (mtHsp70), also known as mortalin, is a protein that in humans is encoded by the ''HSPA9'' gene. Function The product encoded by this gene belongs to the heat shock protein 70 family which contains both ...

and * S100A13 * Synaptotagmin 1 (SYT1)

Function

Interactions

See also

References

Further reading