PDGFC
Encyclopedia
Platelet-derived growth factor C, also known as PDGF-C, is a 345-amino acid protein
that in humans is encoded by the PDGFC gene
. Platelet-derived growth factors are important in connective tissue growth, survival and function, and consist of disulphide-linked dimers involving two polypeptide chains, PDGF-A and PDGF-B. PDGF-C is a member of the PDGF/VEGF family of growth factors with a unique two-domain structure and expression pattern. PDGF-C was not previously identified with PDGF-A and PDGF-B, possibly because it may be that it is synthesized and secreted as a latent growth factor, requiring proteolytic removal of the N-terminal CUB domain for receptor binding and activation.
family. The four members of this family are mitogenic
factors for cells of mesenchymal
origin and are characterized by a core motif of eight cysteines. This gene product appears to form only homodimers. It differs from the platelet-derived growth factor alpha and beta polypeptides in having an unusual N-terminal domain, the CUB domain
.
PDGF-C is a key component of the PDGFR-α
signaling pathway and has a specific role in palatogenesis
and the morphogenesis
of the integumentary
tissue. The phenotypes of compound mutants imply that PDGF-C and PDGF-A may function as principal ligands for PDGFR-α.
Mouse knockout studies show that PDGF-C is required for palatogenesis
. Although human studies support an etiologic role for several genes in CL/P etiology (PVRL1
, IRF6
, and MSX1
), expression levels of the mouse homologs of these genes were unaltered in Pdgfc−/− mutant embryos that develop clefts, suggesting that their activity is not related to PDGF-C signaling in palatogenesis, so PDGF-C signaling is a new pathway in palatogenesis.
with PDGFRA
.
PDGF-C is a latent growth factor with proteolytic activation, and the processing enzyme might be controlled by the other CLP-associated genes that may indirectly connect to PDGF-C signaling. Notably, a 30-cM region on human chromosome 4, where the PDGFC gene maps, shows strong linkage association with CLP26, and clinical genetic data further suggest a potential link between PDGFC gene polymorphism and CLP.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the PDGFC gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Platelet-derived growth factors are important in connective tissue growth, survival and function, and consist of disulphide-linked dimers involving two polypeptide chains, PDGF-A and PDGF-B. PDGF-C is a member of the PDGF/VEGF family of growth factors with a unique two-domain structure and expression pattern. PDGF-C was not previously identified with PDGF-A and PDGF-B, possibly because it may be that it is synthesized and secreted as a latent growth factor, requiring proteolytic removal of the N-terminal CUB domain for receptor binding and activation.
Function
The protein encoded by this gene is a member of the platelet-derived growth factorPlatelet-derived growth factor
In molecular biology, platelet-derived growth factor is one of the numerous growth factors, or proteins that regulate cell growth and division. In particular, it plays a significant role in blood vessel formation , the growth of blood vessels from already-existing blood vessel tissue. Uncontrolled...
family. The four members of this family are mitogenic
Mitogen
A mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein.Mitogenesis is the induction of mitosis, typically via a mitogen....
factors for cells of mesenchymal
Mesenchymal stem cell
Mesenchymal stem cells, or MSCs, are multipotent stem cells that can differentiate into a variety of cell types, including: osteoblasts , chondrocytes and adipocytes...
origin and are characterized by a core motif of eight cysteines. This gene product appears to form only homodimers. It differs from the platelet-derived growth factor alpha and beta polypeptides in having an unusual N-terminal domain, the CUB domain
CUB domain
CUB domain is an evolutionary conserved protein domain.The CUB domain is a structural motif of approximately 110 residues found almost exclusively in extracellular and plasma membrane-associated proteins, many of which are developmentally regulated...
.
PDGF-C is a key component of the PDGFR-α
PDGFRA
Alpha-type platelet-derived growth factor receptor is a protein that in humans is encoded by the PDGFRA gene.-Interactions:PDGFRA has been shown to interact with PDGFRB, PLCG1, Sodium-hydrogen antiporter 3 regulator 1, Cbl gene, CRK, Caveolin 1 and PDGFC.-Further reading:...
signaling pathway and has a specific role in palatogenesis
Secondary palate development
The development of the secondary palate commences in the sixth week of human embryological development. It is characterised by the formation of two palatal shelves on the maxillary prominences, the elevation of these shelves to a horizontal position, and then a process of palatal fusion between the...
and the morphogenesis
Morphogenesis
Morphogenesis , is the biological process that causes an organism to develop its shape...
of the integumentary
Integumentary system
The integumentary system is the organ system that protects the body from damage, comprising the skin and its appendages...
tissue. The phenotypes of compound mutants imply that PDGF-C and PDGF-A may function as principal ligands for PDGFR-α.
Mouse knockout studies show that PDGF-C is required for palatogenesis
Secondary palate development
The development of the secondary palate commences in the sixth week of human embryological development. It is characterised by the formation of two palatal shelves on the maxillary prominences, the elevation of these shelves to a horizontal position, and then a process of palatal fusion between the...
. Although human studies support an etiologic role for several genes in CL/P etiology (PVRL1
PVRL1
Poliovirus receptor-related 1 , also known as PVRL1, is a human gene that encodes a protein of immunoglobulin superfamily also considered a member of the nectins . It is a membrane protein with three extracellular immunoglobulin domains, a single transmembrane helix and a cytoplasmic tail...
, IRF6
IRF6
Interferon regulatory factor 6 also known as IRF6 is a protein that in humans is encoded by the IRF6 gene.-Function:This gene encodes a member of the interferon regulatory transcription factor family...
, and MSX1
MSX1
Msh homeobox 1, also known as MSX1, is a protein that in humans is encoded by the MSX1 gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue that produces both TSHß- and a-subunits and...
), expression levels of the mouse homologs of these genes were unaltered in Pdgfc−/− mutant embryos that develop clefts, suggesting that their activity is not related to PDGF-C signaling in palatogenesis, so PDGF-C signaling is a new pathway in palatogenesis.
Interactions
PDGFC has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with PDGFRA
PDGFRA
Alpha-type platelet-derived growth factor receptor is a protein that in humans is encoded by the PDGFRA gene.-Interactions:PDGFRA has been shown to interact with PDGFRB, PLCG1, Sodium-hydrogen antiporter 3 regulator 1, Cbl gene, CRK, Caveolin 1 and PDGFC.-Further reading:...
.
PDGF-C is a latent growth factor with proteolytic activation, and the processing enzyme might be controlled by the other CLP-associated genes that may indirectly connect to PDGF-C signaling. Notably, a 30-cM region on human chromosome 4, where the PDGFC gene maps, shows strong linkage association with CLP26, and clinical genetic data further suggest a potential link between PDGFC gene polymorphism and CLP.