Protein FLT1

URN urn:agi-llid:2321
Name FLT1
Description FMS-like tyrosine kinase 1
Connectivity 486
Notes A potential mechanism involved in hemangioma formation is the alteration of the FLT1 receptor signaling pathway in endothelial and/or pericytic cells. A potential mechanism involved in hemangioma formation is the alteration of the FLT1 receptor signaling pathway in endothelial and/or pericytic cells. Aberrant methylation of the vascular endothelial growth factor receptor-1 gene is associated with prostate cancer. Blocking VEGF and PDGF receptor signaling in cardiac allografts has distinctive effects on inflammation and survival. C-Myc over-expression was significantly associated with high sVEGF and normal sFlt-1 level in DLBCL patients, suggesting a complex interrelationship between c-Myc oncogene expression and angiogenic regulators. CLL B cells consistently express VEGFR1 mRNA; co-expression of angiogenic molecules and receptors suggest autocrine pathways of stimulation. Data suggest that vascular endothelial growth factor (VEGF) receptor flt-1 is expressed by eosinophils whose activation with VEGF stimulates directed migration and release of eosinophil cationic protein. During tumour progression there is a change in the relative amounts of sFIt-1 and vascular endothelial growth factor in the circulation. Effect of placenta growth factor-1 on proliferation and release of nitric oxide, cyclic AMP and cyclic GMP in human epithelial cells expressing the FLT-1 receptor. Expression of vascular endothelial growth factor and its receptor (Flt-1) in breast carcinoma. Granulocyte-Macrophage Colony-Stimulating Factor and monocytes play a vital role in angiogenesis through the regulation of VEGF and sVEGFR-1. In human umbilical vein endothelial cells, the Flt-1 receptor appears to act as a decoy receptor, tempering the response to lower concentrations of VEGF. In this study we give evidence of Flt-1 and KDR receptors in platelets. In vitro stimulation of blood samples with bacteria-derived antigens resulted in a significant increase in soluble VEGF (p < 0.0001) and a less pronounced but still significant increase in soluble VEGFR1. Increased expression of FLT1 is associated with an aggressive angiogenic phenotype in melanoma. Increased sFlt-1 secretion in first versus second pregnancies may account in part for the increased risk of preeclampsia among nulliparous women. Involvement of VEGFR-2 (kdr/flk-1) but not VEGFR-1 (flt-1) in VEGF-A and VEGF-C-induced tube formation by human microvascular endothelial cells in fibrin matrices in vitro. Oncogene FLT belongs to the src gene family and is related to oncogene ROS (MIM 165020). Like other members of this family, it shows tyrosine protein kinase activity that is important for the control of cell proliferation and differentiation. The sequence structure of the FLT gene resembles that of the FMS gene (MIM 164770); hence, Yoshida et al. (1987) proposed the name FLT as an acronym for FMS-like tyrosine kinase.[supplied by OMIM]. Placental growth factor promotes recruitment of VEGFR1(+) hematopoietic stem cells from a quiescent to a proliferative bone marrow microenvironment, favoring differentiation, mobilization and reconstitution of hematopoiesis. Postmortem brain tissue analysis demonstrates VEGFR1 localized as paracellular deposits in Durck's granulomas of patients with cerebral malaria. Preeclamptic placental villous explants showed a four-fold increase in sVEGFR-1 over normal pregnancies. Elevated levels of sVEGFR-1 in preeclampsia are responsible for inhibiting angiogenesis. Relative to human VEGF165, the binding affinity of Pm venom VEGF to the human VEGFR-1 was 1.7-fold higher while affinity to the VEGFR-2 was 17-fold lower. But it did not bind the VEGFR-3 or neuropilin-1. Specific VEGFR1 expression, examined in 27 B-CLL samples, was positive in all of them. The VEGF transduction pathway may be very active in CLL cells. Both its paracrine & autocrine pathways may contribute to their enhanced survival. Staining for the receptors VEGFR-1 and VEGFR-2 was positive in large lymphoid cells in stage IV non-Hodgkin lymphoma. Subjects with acute mountain sickness have lower levels of soluble VEGF receptor (Flt-1) at both low and high altitude compared with well subjects. The expression of vascular endothelial growth factor and its receptors KDR and Flt-1 by gastric carcinoma tissues and cell lines was detected to elucidate the molecular mechanism of this growth factor in promoting tumor growth. There was a significant positive correlation between the level of expression of VEGF and VEGF-R1 (P = 0.04) in both control groups and lung bearing tumorlets. These data support the involvement in melanoma growth and survival of a VEGF-dependent internal autocrine loop mechanism, at least in vitro. These findings are consistent with the idea that the chemotactic effect of VEGF-A on mesenchymal progenitor cells (MPC) is mediated via VEGFR-1, and that VEGF-A and PlGF-1, have a functional role for recruitment of osteoprogenitor cells. This protein is a novel therapeutic target for angiogenic disorders (REVIEW). Up-regulation of VEGF-A receptor VEGFR-1 in capillaries in menorrhagia could be involved in abnormal endometrial vascular structure and permeability. VEGF and flt-1 are upregulated in blood vessels in many organs of acute Kawasaki Disease. VEGF and sFLT-1 can actively take part in the pathogenesis of diabetic nephropathy. VEGF receotor signaling regulates survival signals in CLL cells and that interruption of this autocrine pathway results in caspase activation and subsequent leukemic cell death. VEGF secreted by retinal pigment epithelial cells upregulates pigment epithelium-derived factor expression via VEGFR-1 in an autocrine manner. VEGF, VEGFR-1 and VEGFR-2 are concomitantly expressed in pre-B ALL cells. Expression of the receptors is limited to the intra-cytoplasmic compartment and may suggest either internalization or a block in trafficking of the receptor to the surface. VEGFR-1 secreted by endothelial cells becomes a matrix-associated protein that is able to interact with the alpha 5 beta 1 integrin; a new role of VEGFR-1 in angiogenesis. VEGFR1 initiates a clonogenic response in myeloid leukemia cells that is PI3-kinase dependent. When used individually, FGFR1 partially prevented goiter and sVEGFR1 partially reduced vascular volume. A basis for understanding molecular recognition between PlGF-1 and VEGFR1. Changing of transcriptional activity of VEGF gene and its receptor FLT-1 indicates an autocrine mechanism of regulation of angiogenic gene activity in the first step of carcinogenesis--low-grade intraepithelial lesions of the uterine cervix. Crystal structure of placental growth factor in complex with domain 2 of vascular endothelial growth factor receptor-1. Cytotrophobasts possess a unique property to enhance sFlt-1 production under reduced oxygen. Expression of VEGF receptor-1 in normal human epidermal keratinocytes; a role for VEGFR-1 in the proliferation of keratinocytes was found. Expression system is involved in angiogenesis in inflamed synovial tissue in the temporomandibular joint. Expression, purification and detection of biological activity. Findings demonstrate a requirement for VEGFR1+ haematopoietic progenitors in the regulation of metastasis, and suggest that expression patterns of fibronectin and VEGFR1+VLA-4+ clusters dictate organ-specific tumour spread. Findings may point to an involvement of soluble vascular endothelial growth factor receptor-1 in the pathophysiology of preeclampsia possibly by antagonizing vascular endothelial growth factor effects. Flt-1 appears to be important in the temporal regulation of oviductal secretion. Fms-like tyrosine kinase 1, a circulating antiangiogenic protein, may play an important role in the pathogenesis of preeclampsia [review]. Fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor). In humans: 1) VEGF, KDR, and Flt-1 mRNA are increased by acute systemic exercise; 2) the time course of the VEGF, KDR, and Flt-1 mRNA responses are different from those previously reported in rats. In systemic lupus erythematosus patients the levels of VEGF and sVEGFR-1 are higher in patients with active SLE than in inactive disease or healthy persons. In vivo EPO does not affect the functionality and/or production of components of the VEGF/Flt-1 system in diabetics with normal or reduced renal function. MRNA expression of VEGF and its receptor flt-1 in the hydrosalpinx was significantly higher than that in the healthy oviduct. Overproduction of soluble VEGFR-1 may lead to suppression of VEGF-A and PlGF and the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, may result in the defective uteroplacental development. Presence of an sVEGFR-1 in human serum and plasma of normal male and female donors strongly suggests that it plays an important role as a naturally occurring VEGF antagonist in the regulation and availability of VEGF-mediated biological activities in vivo. Results suggest that in the hematopoietic microenvironment an autocrine vascular endothelial growth factor loop contributes to optimal megakaryocytic maturation through Flt1. Role for sFlt-1 in the maternal manifestations of preeclampsia. Vitronectin increased the presence of all four growth factor receptors and most notably, VEGFR-1; in contrast, fibrin decreased all four receptors, especially FGFR-1 and FGFR-2.

KEGG pathway Cytokine-cytokine receptor interaction
Focal adhesion

Swiss-Prot Accession B0LPF1
P17948
Q16332
Q16333
Q59GQ9
O55095
P35969
Q3TJC1
Q5GRG7
Q78ZF4
Q8K1H4
Q9CSC8
Q9CW58
Q9DAV2
P53767
Q9JJ08
Q5TAR1

Unigene ID Hs.654360
Mm.389712
Rn.10239
Hs.507621
Mm.3464

KEGG ID rno:54251
hsa:2321
mmu:14254

EC Number 2.7.10.1
2.7.1.112

Swiss-Prot ID VGFR1_HUMAN
VGFR1_RAT
B0LPF1_HUMAN

Cell Localization Plasma membrane

GO ID 0005524
0019838
0042802
0000166
0004872
0016740
0005021
0030154
0016477
0007565
0007275
0001569
0008284
0030949
0006468
0007169
0005576
0005615
0005887
0005886
0016301
0004672
0004713
0004714
0001525
0048010
0016021
0016020
0004716
0000186
0030522
0030335
0048146
0048661
0006940
0001666
0004674

Pathway VEGFR -> CTNNB signaling
VEGFR -> ATF/CREB/ELK-SRF signaling
PPARG Targets
PPARbeta Targets

IPI ID IPI00018335
IPI00216043
IPI00815971
IPI00816497
IPI00124497
IPI00551339
IPI00119072
IPI00212864
IPI00779044

Ariadne Ontology GFR

Mouse chromosome position 5 82.0 cM

GO Molecular Function nucleotide binding
ATP binding
growth factor binding
identical protein binding
transferase activity
kinase activity
protein kinase activity
protein tyrosine kinase activity
receptor signaling protein tyrosine kinase activity
transmembrane receptor protein tyrosine kinase activity
vascular endothelial growth factor receptor activity
receptor activity

Homologene ID 20463

Hugo ID 3763

GO Cellular Component extracellular region
membrane
plasma membrane
integral to membrane
integral to plasma membrane
extracellular space

MGI ID 95558
2140833

Human chromosome position 13q12

GO Biological Process angiogenesis
patterning of blood vessels
positive regulation of cell proliferation
positive regulation of vascular endothelial growth factor receptor signaling pathway
positive regulation of cell migration
positive regulation of smooth muscle cell proliferation
positive regulation of fibroblast proliferation
activation of MAPKK activity
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
intracellular receptor-mediated signaling pathway
regulation of smooth muscle contraction
cell migration
cell differentiation
protein amino acid phosphorylation
multicellular organismal development
female pregnancy
response to hypoxia

Rat chromosome position 12p11

GenBank ID NC_000013
NM_002019
NP_002010
NT_024524
NW_925473
NW_001838071
AC_000056
AC_000145
AL138712
CAI14846
AL139005
CAI17096
CH471075
EAX08431
EAX08432
CS172284
CAJ33638
D00133
BAA00080
AB209050
BAD92287
AF063657
AAC16449
AK292936
BAF85625
AK300392
BAG62125
AK309901
BC029849
BC039007
AAH39007
BE180461
BU151621
CA396081
CR593658
CR606445
CR615327
DA844548
DQ836394
ABI53803
DQ836395
ABI53804
DQ836396
ABI53805
EF491868
ABS32268
EF491869
ABS32269
EF491870
ABS32270
EU360600
ACB05747
EU368830
ACA62948
EU443152
ACA21474
EU826561
ACF47597
EU826562
ACF47598
S77812
AAB34001
S77814
AAB34002
U01134
AAC50060
P17948
Q16332
Q16333
Q59GQ9
NC_000071
NM_010228
NP_034358
NT_039324
NW_001030800
AC_000027
AC122299
AC131730
AF473823
AAQ05293
AJ224863
CH466614
EDL05837
EDL05838
EDL05839
AJ001177
CAA04571
AK004721
BAB23504
AK005502
BAB24084
AK013236
BAB28733
AK035771
AK084177
AK146906
BAE27519
AK167497
BAE39574
AK167596
BC029674
AAH29674
D88689
BAA24498
D88690
BAA24499
L07297
AAA40078
X78568
CAA55311
O55095
P35969
Q3TJC1
Q5GRG7
Q78ZF4
Q8K1H4
Q9CSC8
Q9CW58
Q9DAV2
NC_005111
NM_019306
NP_062179
NW_047366
NW_001084671
AC_000080
CH474012
EDL89555
EDL89556
AF157595
AAF80356
D28498
BAA05857
P53767
Q9JJ08
Q5TAR1
CAI17097
NW_000248

Group GFR
extracellular region
membrane
plasma membrane
integral to membrane
integral to plasma membrane
extracellular space
nucleotide binding
ATP binding
growth factor binding
identical protein binding
transferase activity
kinase activity
protein kinase activity
protein tyrosine kinase activity
receptor signaling protein tyrosine kinase activity
transmembrane receptor protein tyrosine kinase activity
vascular endothelial growth factor receptor activity
receptor activity
angiogenesis
patterning of blood vessels
positive regulation of cell proliferation
positive regulation of vascular endothelial growth factor receptor signaling pathway
positive regulation of cell migration
positive regulation of smooth muscle cell proliferation
positive regulation of fibroblast proliferation
activation of MAPKK activity
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
intracellular receptor-mediated signaling pathway
regulation of smooth muscle contraction
cell migration
cell differentiation
protein amino acid phosphorylation
multicellular organismal development
female pregnancy
response to hypoxia

RGD ID 2621

LocusLink ID 2321
14254
54251
100598

Alias FLT
VEGFR1
FMS-related tyrosine kinase 1
Flt-1
sFlt1
VEGFR-1
AI323757
OTTMUSP00000023727
vascular permeability factor receptor
vascular endothelial growth factor receptor
vascular endothelial growth factor receptor-1
FMS-like tyrosine kinase 1
Fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)
Flt1
Tyrosine-protein kinase receptor FLT
Vascular endothelial growth factor receptor 1
VEGF receptor
VGR1_HUMAN
FMS-like tyrosine kinase I
fms-related tyrosine kinase I
VEGF receptor I
Vascular endothelial growth factor receptor I
VEGF-R1
Flt I
sFlt I
VEGFR I
Vascular endothelial growth factor precursor receptors
VEGF receptor 1
Tyrosine- protein kinase FRT
Vascular permeability factor receptors
VEGF receptors
FRT
soluble VEGF receptor 1-14
soluble VEGFR1 variant 2
soluble VEGFR1 variant 21
vascular endothelial growth factor/vascular permeability factor receptor
VEGFR-1s
VEGFR Is

Organism Homo sapiens
Mus musculus
Rattus norvegicus

OMIM ID 165070