This is the first blog post in the series of blog posts that will be focused on the FLT3 gene, FLT3 gene mutations, and functional consequences associated with the FLT3 gene mutations.
In this first post, I will give you a short overview of the FLT3 gene and its role. This blog post is followed by two other posts, each covering specific FLT3-related topics. Here are links to all three blog posts:
What is the FLT3 gene? What does the FLT3 gene encode?
The FLT-3 gene is a protein-coding gene that encodes the Fms-Related Tyrosine Kinase 3, abbreviated as FLT-3, also known as a cluster of differentiation antigen 135 (CD135) [citation]. If you are interested in what the cluster of differentiation is, please check this article.
Who discovered the FLT3 gene?
The FLT-3 gene was discovered by two independent groups in 1991:
Matthews et al. discovered a novel receptor tyrosine kinase in murine (mouse) cells, called at that time fetal liver kinase-2 or flk-2, which was discussed to be an essential signal-transducing molecule in early totipotent hematopoietic stem cells [citation]. Totipotent hematopoietic stem cells are characterized by the ability to give rise to blood cell types that are more differentiated (different cells that constitute the blood). You can check my short definition article about totipotent hematopoietic stem cells here.
Rosnet et al. showed that this novel receptor tyrosine kinase was expressed mainly in the placenta, in adult tissues, including gonads and the brain, and in hematopoietic cells [citation].
On what chromosome is the FLT3 gene located?
The FLT-3 gene is on chromosome 13 (position 13q12.2), roughly 993 amino acids [citation].
What is the function of the FLT3 gene? What does the FLT3 protein (Fms-Related Tyrosine Kinase 3) do? What is the function of Fms-Related Tyrosine Kinase 3?
As mentioned above, the FLT-3 gene encodes a protein which is Fms-Related Tyrosine Kinase 3. Fms-Related Tyrosine Kinase 3 is a signal-transducing molecule and a member of a larger group of proteins called receptor tyrosine kinases (RTKs). As far as I could find, the abbreviation FMS should refer to Fetal Membranes, but I am not entirely sure on this.
The FL protein or Fms-Related Tyrosine Kinase 3 Ligand (FLT3L) binds to Fms-Related Tyrosine Kinase 3. The FL protein is a type of growth factor bound to a membrane found in the hematopoietic bone marrow microenvironment [citation, citation], but more about this later.
As already mentioned, Fms-Related Tyrosine Kinase 3 is a member of a larger group of proteins called receptor tyrosine kinases (RTKs), which is expressed on the membrane of cells, mostly CD34+ hematopoietic stem cells and immature hematopoietic progenitors such as B-lymphoid progenitors, the myeloid precursors and monocytes [citation]. You can check a bit more about kinases, tyrosine kinases, and receptor tyrosine kinases here.
Like other receptor tyrosine kinases, Fms-Related Tyrosine Kinase 3 is a critical signal-transducing molecule. Fms-Related Tyrosine Kinase 3 binds the FL protein, a type of growth factor bound to the cell membrane found in the hematopoietic bone marrow microenvironment [citation], which can also exist in its soluble form (not bound to the membrane). Both forms can activate the tyrosine kinase [citation].
If you would like to read more about the FL protein (FLT3L), please check this post.
The binding of the FL protein-ligand to the receptor causes phosphorylation of the kinase and its activation, which further promotes signal transduction and activation of another critical cellular, and molecular pathways such as:
PI3K pathway
RAS pathway
further activation of AKT (protein kinase B, PKB)
signal transducer and activator transcription factor (STAT) and
extracellular-signal-regulated kinase 1 and 2 (ERK1/2) [citation].
A bit more about phosphorylation I will soon write in a separate article. The above-listed pathways contribute further to cellular proliferation, cell survival, and transcription of apoptotic genes. Apoptotic genes lead to cellular apoptosis - programmed cell death. A bit more about apoptosis I will soon write in a separate article.
Is FLT3 a growth factor?
As explained above, the Fms-Related Tyrosine Kinase 3 is not a growth factor; however, the FL protein (FLT3L) (mentioned above) that binds to Fms-Related Tyrosine Kinase 3 is a growth factor.
This protein’s name is Fms-like tyrosine kinase 3 ligand (FLT3L), an essential regulator of hematopoiesis. Hematopoiesis is the biological process that corresponds to the formation of blood cellular components). I wrote a short article about the FLT3L protein that you can check here.
Is FLT3 a kinase?
Yes, Fms-Related Tyrosine Kinase 3 is a tyrosine kinase, and it is a member of a larger group of proteins called receptor tyrosine kinases (RTKs), which are expressed on the membrane of cells, primarily CD34+ hematopoietic stem cells and immature hematopoietic progenitors such as B-lymphoid progenitors, the myeloid precursors, and monocytes [citation].
Is FLT3 a proto-oncogene?
The FLT-3 gene can be considered a proto-oncogene, as it is a gene that is vital for normal cellular function, which, when mutated, becomes an oncogene, promoting aberrant cell function and oncogenicity. If you want to learn a bit more about what is oncogene and proto-oncogene, check this article.
What is the FLT3 wild type?
The FLT-3 wild-type gene is the normal (non-mutated) variant of the FLT3 gene, occurring in the general population.
If you would like to read more about FLT3 gene mutations and functional consequences associated with the FLT3 gene mutations, please check the other two blog posts: