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 regu ...
and
signaling protein
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
encoded by the ''FGF1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
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 alw ...
17-18 kDa protein.
Fibroblast growth factor
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in the ...
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
S100 calcium-binding protein A13 (S100A13) is a protein that in humans is encoded by the ''S100A13'' gene.
Function
The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 ...
and
Syt1
Synaptotagmin-1 is a protein that in humans is encoded by the ''SYT1'' gene.
Function
Synaptotagmins are integral membrane proteins of synaptic vesicles thought to serve as sensors for calcium ions (Ca2+) in the process of vesicular trafficking ...
) 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
In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization.
Classification
Mo ...
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 as 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, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
. 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 o ...
(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
Fibroblast growth factor 2, also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the ''FGF2'' gene. It binds to and exerts effects via specific fibroblast growth factor receptor ''(FG ...
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 mechanism of action of a ...
and cell survival activities, and are involved in a variety of biological processes, including
embryonic development
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
,
cell growth
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...
,
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 devel ...
,
tissue repair
Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biologi ...
, 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 E ...
- 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 orga ...
. 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
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
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 transcri ...
[
* ]CSNK2B
Casein kinase II subunit beta is a protein that in humans is encoded by the ''CSNK2B'' gene.
This gene encodes the beta subunit of casein kinase II, a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcriptio ...
* CSNK2A1[
* ]FIBP
Acidic fibroblast growth factor intracellular-binding protein is a protein that in humans is encoded by the ''FIBP'' gene.
Function
Acidic fibroblast growth factor is mitogenic for a variety of different cell types and acts by stimulating mitog ...
* FGFR1
Fibroblast growth factor receptor 1 (FGFR1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD331, is a receptor tyrosine kinase whose ligands are specific members of the fibroblast ...
* FGFR2
Fibroblast growth factor receptor 2 (FGFR2) 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.
The protein ...
* FGFR3
Fibroblast growth factor receptor 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 q16.3, is expressed in ...
* FGFR4
Fibroblast growth factor receptor 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 growth fact ...
* 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 h ...
and
* S100A13
S100 calcium-binding protein A13 (S100A13) is a protein that in humans is encoded by the ''S100A13'' gene.
Function
The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 ...
* Synaptotagmin 1 (SYT1)
See also
* Fibroblast growth factor
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in the ...
References
Further reading
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{{Growth factor receptor modulators