Janus kinase 2 is a human protein that has been implicated in signaling by members of the type II cytokine receptor

Type II cytokine receptor

Type II cytokine receptors are transmembrane proteins that are expressed on the surface of certain cells, which bind and respond to a select group of cytokines...

 family (e.g. interferon

Interferon

Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...

 receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g. IL-6R), and the single chain receptors (e.g. Epo-R, Tpo-R, GH-R, PRL-R). JAK2 signaling is activated downstream from the prolactin

Prolactin

Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...

 receptor.

Loss of Jak2 is lethal by embryonic day 12 in mice.

JAK2 orthologs  have been identified in all mammals for which complete genome data are available.

Clinical significance

JAK2 gene fusions with the TEL(ETV6) (TEL-JAK2

TEL-JAK2

TEL-JAK2 is a gene fusion resulting from a chromosomal translocation between chromosomes 9 and 12 observed in human leukemia . The 5' moiety of TEL is fused to the 3' end of JAK2....

) and PCM1 genes have been found in leukemia

Leukemia

Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

 patients.
Mutations in JAK2 have been implicated in polycythemia vera

Polycythemia vera

Polycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the...

, essential thrombocythemia, myelofibrosis

Myelofibrosis

Myelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow...

 as well as other myeloproliferative disorders. This mutation, (V617F) a change of valine

Valine

Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...

 to phenylalanine

Phenylalanine

Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

 at the 617 position, appears to render hematopoietic cells more sensitive to growth factors such as erythropoietin

Erythropoietin

Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...

 and thrombopoietin

Thrombopoietin

Thrombopoietin also known as megakaryocyte growth and development factor is a protein that in humans is encoded by the THPO gene....

.

Interactions

Janus kinase 2 has been shown to interact

Protein-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 Growth hormone receptor

Growth hormone receptor

Growth hormone receptor is a protein that in humans is encoded by the GHR gene. GHR orthologs have been identified in most mammals.-Interactions:...

, Protein arginine methyltransferase 5

Protein arginine methyltransferase 5

Protein arginine N-methyltransferase 5 is an enzyme that in humans is encoded by the PRMT5 gene.-Interactions:Protein arginine methyltransferase 5 has been shown to interact with WD repeat-containing protein 77, CLNS1A, Janus kinase 2, SNRPD3 and SUPT5H.-Further reading:...

, STAT5A

STAT5A

Signal transducer and activator of transcription 5A is a protein that in humans is encoded by the STAT5A gene. STAT5A orthologs have been identified in several placentals for which complete genome data are available.-Interactions:...

, STAT5B

STAT5B

Signal transducer and activator of transcription 5B is a protein that in humans is encoded by the STAT5B gene. STAT5B orthologs have been identified in most placentals for which complete genome data are available.-Interactions:...

, Interleukin 12 receptor, beta 2 subunit

Interleukin 12 receptor, beta 2 subunit

Interleukin 12 receptor, beta 2 subunit is a subunit of the interleukin 12 receptor. IL12RB2 is its human gene. IL12RB2 orthologs have been identified in all mammals for which complete genome data are available.-Interactions:...

, PIK3R1

PIK3R1

Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.-Interactions:PIK3R1 has been shown to interact with EPH receptor A2, KHDRBS1, Lymphocyte cytosolic protein 2, Janus kinase 2, GAB2, CD117, BCAR1, CD28, SHB, EZR, PIK3CD, GAB1, HRAS,...

, SH2B1

SH2B1

SH2B adapter protein 1 is a protein that in humans is encoded by the SH2B1 gene.-Interactions:SH2B1 has been shown to interact with Insulin receptor, Grb2, TrkA and Janus kinase 2.- Clinical significance :...

, SHC1

SHC1

SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene. SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells....

, TEC

TEC (gene)

Tyrosine-protein kinase Tec is an enzyme that in humans is encoded by the TEC gene.-Interactions:TEC has been shown to interact with GNA12, Janus kinase 2, CD117, Suppressor of cytokine signaling 1, ARHGEF12 and DOK1.-Further reading:...

, SOCS3

SOCS3

Suppressor of cytokine signaling 3 is a protein that in humans is encoded by the SOCS3 gene.-Interactions:SOCS3 has been shown to interact with PTPN11, Glycoprotein 130, Erythropoietin receptor, Janus kinase 2, RAS p21 protein activator 1 and Insulin-like growth factor 1 receptor.-Regulation:There...

, PTPN11

PTPN11

Tyrosine-protein phosphatase non-receptor type 11 also known as protein-tyrosine phosphatase 1D or protein-tyrosine phosphatase 2C is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase Shp2.PTPN11 is a member of the protein tyrosine phosphatase ...

, PTPN6

PTPN6

Tyrosine-protein phosphatase non-receptor type 6 is an enzyme that in humans is encoded by the PTPN6 gene.Also known as Src homology region 2 domain-containing phosphatase-1 .-Interactions:...

, Interleukin 5 receptor alpha subunit

Interleukin 5 receptor alpha subunit

Interleukin 5 receptor, alpha also known as CD125 is a subunit of the Interleukin-5 receptor. IL5RA also denotes its human gene.-Interactions:...

, Grb2

Grb2

Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....

, Suppressor of cytokine signaling 1

Suppressor of cytokine signaling 1

Suppressor of cytokine signaling 1 is a protein that in humans is encoded by the SOCS1 gene. SOCS1 orthologs have been identified in several mammals for which complete genome data are available.-Interactions:...

, VAV1

VAV1

Proto-oncogene vav is a protein that in humans is encoded by the VAV1 gene.-Interactions:VAV1 has been shown to interact with Ku70, PLCG1, Lymphocyte cytosolic protein 2, Janus kinase 2, SIAH2, S100B, Abl gene, ARHGDIB, SHB, PIK3R1, PRKCQ, Grb2, MAPK1, Syk, Linker of activated T cells, Cbl gene and...

, FYN

FYN

Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth...

, Epidermal growth factor receptor

Epidermal growth factor receptor

The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...

, PTK2

PTK2

PTK2 protein tyrosine kinase 2 , also known as Focal Adhesion Kinase , is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes...

, TNFRSF1A

TNFRSF1A

Tumor necrosis factor receptor superfamily member 1A is a protein that in humans is encoded by the TNFRSF1A gene. The protein encoded by this gene is a member of the Tumor necrosis factor receptor superfamily, which also contains TNFRSF1B. This protein is one of the major receptors for the tumor...

, Erythropoietin receptor

Erythropoietin receptor

The erythropoietin receptor is a protein that in humans is encoded by the EPOR gene. EpoR is a 59 kDa peptide and is a member of the cytokine receptor family. EpoR pre-exists as dimers...

, YES1

YES1

Proto-oncogene tyrosine-protein kinase Yes is an enzyme that in humans is encoded by the YES1 gene.-Interactions:YES1 has been shown to interact with Janus kinase 2, CTNND1, RPL10 and Occludin.-Further reading:...

, IRS1

IRS1

Insulin receptor substrate 1 is a protein that in humans is encoded by the IRS-1 gene.-Function:Insulin receptor substrate 1 plays a key role in transmitting signals from the insulin and insulin-like growth factor-1 receptors to intracellular pathways PI3K / Akt and Erk MAP kinase...

, DNAJA3

DNAJA3

DnaJ homolog subfamily A member 3, mitochondrial is a protein that in humans is encoded by the DNAJA3 gene.-Interactions:DNAJA3 has been shown to interact with HSPA8, RAS p21 protein activator 1 and Janus kinase 2.-Further reading:...

, Signal transducing adaptor molecule and PPP2R4

PPP2R4

Serine/threonine-protein phosphatase 2A regulatory subunit B is an enzyme that in humans is encoded by the PPP2R4 gene.-Interactions:PPP2R4 has been shown to interact with PPP2R3A, CCNG1 and Janus kinase 2.-Further reading:...

.

Further reading

External links