BNP

https://www.uniprot.org/uniprotkb/P16860/entry

Brain natriuretic peptide 32
Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:9458824, PubMed:1672777, PubMed:1914098, PubMed:17372040).
May also function as a paracrine antifibrotic factor in the heart (By similarity).
Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins that drive various biological responses (PubMed:9458824, PubMed:1672777, PubMed:17372040, PubMed:21098034, PubMed:17349887, PubMed:25339504).
Involved in regulating the extracellular fluid volume and maintaining the fluid-electrolyte balance through natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion (PubMed:9458824, PubMed:1914098).
Binds the clearance receptor NPR3 (PubMed:16870210).By Similarity8 Publications
NT-proBNP
May affect cardio-renal homeostasis (PubMed:17372040).
Able to promote the production of cGMP although its potency is very low compared to brain natriuretic peptide 32 (PubMed:17372040).1 Publication
BNP(3-32)
May have a role in cardio-renal homeostasis (PubMed:17372040).
Able to promote the production of cGMP (PubMed:17372040).
Miscellaneous
Plasma levels of natriuretic peptides B, brain natriuretic peptide 32 and NT-proBNP are widely used for screening and diagnosis of heart failure (HF), as these markers are typically higher in patients with severe HF.5 Publications
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Post-translational modification
The precursor molecule is proteolytically cleaved by the endoproteases FURIN or CORIN at Arg-102 to produce brain natriuretic peptide 32 and NT-proBNP (PubMed:21314817, PubMed:10880574, PubMed:21763278, PubMed:20489134, PubMed:21482747).
This likely occurs after it has been secreted into the blood, either during circulation or in the target cells (PubMed:21482747).
CORIN also cleaves the precursor molecule at additional residues including Arg-99 and possibly Lys-105 (PubMed:20489134, PubMed:21763278).
In patients with heart failure, processing and degradation of natriuretic peptides B occurs but is delayed, possibly due to a decrease in enzyme level or activity of CORIN and DPP4 (PubMed:25339504).6 Publications
Brain natriuretic peptide 32
Undergoes further proteolytic cleavage by various proteases such as DPP4, MME and possibly FAP, to give rise to a variety of shorter peptides (PubMed:16254193, PubMed:19808300, PubMed:21314817, PubMed:21098034).
Cleaved at Pro-104 by the prolyl endopeptidase FAP (seprase) activity (in vitro) (PubMed:21314817).
Degraded by IDE (PubMed:21098034).
During IDE degradation, the resulting products initially increase the activation of NPR1 and can also stimulate NPR2 to produce cGMP before the fragments are completely degraded and inactivated by IDE (in vitro) (PubMed:21098034).4 Publications
O-glycosylated on at least seven residues (PubMed:20489134, PubMed:21763278, PubMed:16750161, PubMed:17349887, PubMed:21482747).
In cardiomyocytes, glycosylation at Thr-97 is essential for the stability and processing of the extracellular natriuretic peptides B (PubMed:21482747).
Glycosylation, especially at Thr-97, may also be important for brain natriuretic peptide 32 stability and/or extracellular distribution (PubMed:21763278).
Glycosylation at Thr-97 appears to inhibit FURIN- or CORIN-mediated proteolytic processing, at least in HEK293 cells (PubMed:20489134, PubMed:21763278).5 Publications

Conversion of Brain natriuretic peptide

Neprilysin

https://www.uniprot.org/uniprotkb/P08473/entry

Function

Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:6349683, PubMed:6208535, PubMed:15283675, PubMed:8168535).
Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:6349683, PubMed:17101991).
Catalyzes cleavage of bradykinin, substance P and neurotensin peptides (PubMed:6208535).
Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:6349683, PubMed:15283675).
Involved in the degradation of atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1-32)) (PubMed:2531377, PubMed:2972276, PubMed:16254193).
Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573).8 Publications

Miscellaneous

Important cell surface marker in the diagnostic of human acute lymphocytic leukemia.3 Publications

Catalytic activity

Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.5 Publications
EC:3.4.24.11 (UniProtKB | ENZYME | Rhea)

Activity regulation

Inhibited in a dose dependent manner by opiorphin (PubMed:17101991).
Activated by K49-P1-20, a twenty-residue synthetic peptide shortened from the snake B.asper myotoxin II (PubMed:26931059).

Furin

https://www.uniprot.org/uniprotkb/P09958/entry

Function

function
Ubiquitous endoprotease within constitutive secretory pathways capable of cleavage at the RX(K/R)R consensus motif (PubMed:11799113, PubMed:1629222, PubMed:1713771, PubMed:2251280, PubMed:24666235, PubMed:25974265, PubMed:7592877, PubMed:7690548, PubMed:9130696).
Mediates processing of TGFB1, an essential step in TGF-beta-1 activation (PubMed:7737999).
Converts through proteolytic cleavage the non-functional Brain natriuretic factor prohormone into its active hormone BNP(1-32) (PubMed:20489134, PubMed:21763278).
By mediating processing of accessory subunit ATP6AP1/Ac45 of the V-ATPase, regulates the acidification of dense-core secretory granules in islets of Langerhans cells (By similarity).By Similarity12 Publications
(Microbial infection) Cleaves and activates diphtheria toxin DT.1 Publication
(Microbial infection) Cleaves and activates anthrax toxin protective antigen (PA).2 Publications
(Microbial infection) Cleaves and activates HIV-1 virus Envelope glycoprotein gp160.1 Publication
(Microbial infection) Required for H7N1 and H5N1 influenza virus infection probably by cleaving hemagglutinin.1 Publication
(Microbial infection) Able to cleave S.pneumoniae serine-rich repeat protein PsrP.1 Publication
(Microbial infection) Facilitates human coronaviruses EMC and SARS-CoV-2 infections by proteolytically cleaving the spike protein at the monobasic S1/S2 cleavage site. This cleavage is essential for spike protein-mediated cell-cell fusion and entry into human lung cells.2 Publications
(Microbial infection) Facilitates mumps virus infection by proteolytically cleaving the viral fusion protein F.1 Publication

Catalytic activity

Release of mature proteins from their proproteins by cleavage of -Arg-Xaa-Yaa-Arg-|-Zaa- bonds, where Xaa can be any amino acid and Yaa is Arg or Lys. Releases albumin, complement component C3 and von Willebrand factor from their respective precursors.16 Publications
EC:3.4.21.75 (UniProtKB | ENZYME | Rhea)

Cofactor

Ca2+ (UniProtKB | Rhea| CHEBI:29108 )4 Publications
Note: Binds 3 calcium ions per subunit.3 Publications

Activity regulation

Inhibited by the not secondly cleaved propeptide (PubMed:9130696, PubMed:11799113).
Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl-phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148) (PubMed:24666235, PubMed:25974265).
Inhibited by Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl-RVKR-CMK) (PubMed:32362314).
Inhibited by heparin/heparan sulfate-binding (PubMed:2408021).6 Publications
pH Dependence
Optimum pH is 6.0.1 Publication

Atrial natriuretic peptide-converting enzyme

https://www.uniprot.org/uniprotkb/Q9Y5Q5/entry

Alternative names

Corin
Heart-specific serine proteinase ATC2
Pro-ANP-converting enzyme
Transmembrane protease serine 10

Function
function
Serine-type endopeptidase involved in atrial natriuretic peptide (NPPA) and brain natriuretic peptide (NPPB) processing (PubMed:10880574, PubMed:21288900, PubMed:20489134, PubMed:21763278).
Converts through proteolytic cleavage the non-functional propeptides NPPA and NPPB into their active hormones, ANP and BNP(1-32) respectively, thereby regulating blood pressure in the heart and promoting natriuresis, diuresis and vasodilation (PubMed:10880574, PubMed:21288900, PubMed:20489134, PubMed:21763278).
Proteolytic cleavage of pro-NPPA also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus (PubMed:22437503).
Also acts as a regulator of sodium reabsorption in kidney (By similarity).By Similarity5 Publications
Isoform 2
Has weaker endopeptidase activity compared to isoform 1.
Miscellaneous
Initially named CORIN due to its abundant expression in the heart.1 Publication
Activity regulation
Inhibited in a dose-dependent manner by non-specific trypsin-like serine protease inhibitors including benzamidine.

Mast/stem cell growth factor receptor Kit

https://www.uniprot.org/uniprotkb/P10721/entry
Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.10 Publications
Miscellaneous
Numerous proteins are phosphorylated in response to KIT signaling, but it is not evident to determine which are directly phosphorylated by KIT under in vivo conditions.

Activity regulation

Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Activity is down-regulated by PRKCA-mediated phosphorylation on serine residues. Inhibited by imatinib/STI-571 (Gleevec) and sunitinib; these compounds maintain the kinase in an inactive conformation.

Protein names

Recommended name
Mast/stem cell growth factor receptor Kit
EC number
EC:2.7.10.1 (UniProtKB | ENZYME | Rhea)
Short names
SCFR
Alternative names
Piebald trait protein (PBT)
Proto-oncogene c-Kit
Tyrosine-protein kinase Kit
p145 c-kit
v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
CD Antigen Name
CD117

Gastrointestinal stromal tumor (GIST)

4 Publications
Note
The gene represented in this entry is involved in disease pathogenesis
Description
Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery.
See also
MIM:606764

Testicular germ cell tumor (TGCT)

Note
The gene represented in this entry may be involved in disease pathogenesis
Description
A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.
See also
MIM:273300
Leukemia, acute myelogenous (AML)
Note
The gene represented in this entry is involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase
Description
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
See also
MIM:601626

Proto-oncogene tyrosine-protein kinase receptor Ret

https://www.uniprot.org/uniprotkb/P07949/entry
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways (PubMed:28846097, PubMed:28953886, PubMed:28846099).
Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL (PubMed:28846099).

Involvement in disease

Colorectal cancer (CRC)
Note
The disease may be caused by variants affecting the gene represented in this entry
Description
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
See also
MIM:114500
Hirschsprung disease 1 (HSCR1)
17 Publications
Note
The disease is caused by variants affecting the gene represented in this entry
Description
A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child.
See also
MIM:142623
Medullary thyroid carcinoma (MTC)
20 Publications
Note
The disease is caused by variants affecting the gene represented in this entry
Description
Rare tumor derived from the C cells of the thyroid. Three hereditary forms are known, that are transmitted in an autosomal dominant fashion: (a) multiple neoplasia type 2A (MEN2A), (b) multiple neoplasia type IIB (MEN2B) and (c) familial MTC (FMTC), which occurs in 25-30% of MTC cases and where MTC is the only clinical manifestation.
See also
MIM:155240
Multiple neoplasia 2B (MEN2B)
7 Publications
Note
The disease is caused by variants affecting the gene represented in this entry
Description
Uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophthalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases.
See also
MIM:162300
Pheochromocytoma (PCC)
1 Publication
Note
Disease susceptibility is associated with variants affecting the gene represented in this entry
Description
A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.
See also
MIM:171300
Multiple neoplasia 2A (MEN2A)
12 Publications
Note
The disease is caused by variants affecting the gene represented in this entry
Description
The most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism.
See also
MIM:171400
Various chromosomal aberrations involving RET are known. Some of them have been found in papillary thyroid carcinomas (PTCs) (PubMed:12787916, PubMed:2406025, PubMed:10980597, PubMed:10439047). Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene (PubMed:2406025). Inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene. Translocation t(10;14)(q11;q32) with GOLGA5 generates the RET/GOLGA5 (PTC5) oncogene (PubMed:2734021). Translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET fusion (PubMed:10980597). Translocation t(6;10)(p21.3;q11.2) with TRIM27/RFP generates the Delta RFP/RET oncogene (PubMed:12787916). Translocation t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene (PubMed:10439047). Translocation t(7;10)(q32;q11) with TRIM24/TIF1 generates the TRIM24/RET (PTC6) oncogene (PubMed:10439047). Translocation t(6;10)(p21.3;q11.2) with TRIM27/RFP generates the TRIM27/RET oncogene (PubMed:3037315)6 Publications
Mutations in RET have been detected in patients with renal agenesis suggesting a possible involvement of this gene in disease pathogenesis

FLT-3 (Fms-like tyrosine kinase 3)

https://www.uniprot.org/uniprotkb/P36888/entry
Stem cell tyrosine kinase 1
CD135

Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.
Activity regulation
Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation.

Leukemia, acute myelogenous (AML)

8 Publications
Note
The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase
Description
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
See also
MIM:601626

Fms-related tyrosine kinase 3 ligand

Stimulates the proliferation of early hematopoietic cells by activating FLT3. Synergizes well with a number of other colony stimulating factors .

ブルトン型チロシンキナーゼ Tyrosine-protein kinase BTK

https://www.uniprot.org/uniprotkb/Q06187/entry

Function

Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921).
Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:19290921).
After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members (PubMed:11606584).
PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (PubMed:11606584).
BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (PubMed:16517732, PubMed:17932028).
Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway (PubMed:16517732).
The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (PubMed:16517732).
Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (PubMed:16517732, PubMed:17932028).
Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (PubMed:16415872).
BTK also plays a critical role in transcription regulation (PubMed:19290921).
Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (PubMed:19290921).
BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921).
Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188).
Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:9012831).
GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:9012831).
ARID3A and NFAT are other transcriptional target of BTK (PubMed:16738337).
BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:16738337).
There is however no evidence that BTK itself binds directly to DNA (PubMed:16738337).
BTK has a dual role in the regulation of apoptosis (PubMed:9751072).

Activity regulation

Activated by phosphorylation. In primary B lymphocytes, is almost always non-phosphorylated and is thus catalytically inactive. Stimulation of TLR8 and TLR9 causes BTK activation. As a negative feedback mechanism to fine-tune BCR signaling, activated PRKCB down-modulates BTK function via direct phosphorylation of BTK at Ser-180, resulting in translocation of BTK back to the cytoplasmic fraction. PIN1, SH3BP5, and IBTK were also identified as BTK activity inhibitors. Interaction with CAV1 leads to dramatic down-regulation of the kinase activity of BTK. LFM-13A is a specific inhibitor of BTK. Dasatinib, a cancer drug acting as a tyrosine kinase inhibitor, also blocks BTK activity.

Receptor-type tyrosine-protein kinase FLT3

https://www.uniprot.org/uniprotkb/P36888/entry
FL cytokine receptor
Fetal liver kinase-2 (FLK-2)
Fms-like tyrosine kinase 3 (FLT-3)
Stem cell tyrosine kinase 1 (STK-1)
CD Antigen Name
CD135

Function

function
Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.

Activity regulation

Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation.2 Publications

Involvement in disease

Leukemia, acute myelogenous (AML)
8 Publications
Note
The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase
Description
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.