PSTPIP2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | PSTPIP2 , MAYP, proline-serine-threonine phosphatase interacting protein 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 616046 MGI: 1335088 HomoloGene: 69150 GeneCards: PSTPIP2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Proline-serine-threonine phosphatase-interacting protein 2 is an enzyme that in humans is encoded by the PSTPIP2 gene. [4] [5] This protein, also known as macrophage F-actin-associated and tyrosine phosphorylated protein (MAYP) is a member of the Pombe Cdc15 homology (PCH) family of proteins has been shown to coordinate membrane and cytoskeletal dynamics [6]
Pstpip2 is selectively expressed in macrophages and macrophage precursors, [7] [8] and it is an actin bundling protein which regulates filopodia formation and macrophage motility [9]
PSTPIP2 deficiency leads to elevated levels of circulating inflammatory mediators in vivo. In asymptomatic mice, only MIP-1α and IL-6 are elevated, however symptomatic PSTPIP2-deficient mice have elevated levels of circulating IL-6, MIP-1α, TNF-α, CSF-1 and IP-10 [10] and decreased levels of IL-13 [11] [12]
The missense mutation I282N leads to a macrophage-mediated autoinflammatory disease called Lupo Pstpip2 (Pstpip2Lupo/Lupo ). It is characterized by skin necrosis, inflammation of paws, ears and inflammatory bone resorption. [8] Another mutation in Pstpip2, L98P, was described in chronic multifocal osteomyelitis (cmo) mice. This disease is also autoinflammatory, and causes inflammatory infiltrate of polymorphonuclear leukocytes, macrophages, lymphocytes, plasma cells and osteoclasts. Later the infiltrate is replaced with new bone tissue which lead to tail kinks and hind-foot deformities. The cmo mice also develop ear inflammation in the epidermis, dermis and cartilage. [13]
PSTPIP2 interacts with protein tyrosine phosphatases from the proline-, glutamic acid-, serine- and threonine-rich (PEST) family, [14] SHIP1 and Csk [15]
The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through the process of transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors. Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.
The colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. It is one of the three experimentally described colony-stimulating factors. M-CSF binds to the colony stimulating factor 1 receptor. It may also be involved in development of the placenta.
Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase (PTP) Shp2.
Tyrosine-protein kinase SYK, also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the SYK gene.
Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the TYK2 gene.
Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the PDGFRB gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies.
Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B (PTP1B) is an enzyme that is the founding member of the protein tyrosine phosphatase (PTP) family. In humans it is encoded by the PTPN1 gene. PTP1B is a negative regulator of the insulin signaling pathway and is considered a promising potential therapeutic target, in particular for treatment of type 2 diabetes. It has also been implicated in the development of breast cancer and has been explored as a potential therapeutic target in that avenue as well.
Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115, is a cell-surface protein encoded by the human CSF1R gene. CSF1R is a receptor that can be activated by two ligands: colony stimulating factor 1 (CSF-1) and interleukin-34 (IL-34). CSF1R is highly expressed in myeloid cells, and CSF1R signaling is necessary for the survival, proliferation, and differentiation of many myeloid cell types in vivo and in vitro. CSF1R signaling is involved in many diseases and is targeted in therapies for cancer, neurodegeneration, and inflammatory bone diseases.
Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a cytoplasmatic protein encoded by gene PTPN22 and a member of PEST family of protein tyrosine phosphatases. This protein is also called "PEST-domain Enriched Phosphatase" ("PEP") or "Lymphoid phosphatase" ("LYP"). The name LYP is used strictly for the human protein encoded by PTPN22, but the name PEP is used only for its mouse homolog. However, both proteins have similar biological functions and show 70% identity in amino acid sequence. PTPN22 functions as a negative regulator of T cell receptor (TCR) signaling, which maintains homeostasis of T cell compartment.
Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1(SHIP1) is an enzyme with phosphatase activity. SHIP1 is structured by multiple domain and is encoded by the INPP5D gene in humans. SHIP1 is expressed predominantly by hematopoietic cells but also, for example, by osteoblasts and endothelial cells. This phosphatase is important for the regulation of cellular activation. Not only catalytic but also adaptor activities of this protein are involved in this process. Its movement from the cytosol to the cytoplasmic membrane, where predominantly performs its function, is mediated by tyrosine phosphorylation of the intracellular chains of cell surface receptors that SHIP1 binds. Insufficient regulation of SHIP1 leads to different pathologies.
Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons.
Receptor-type tyrosine-protein phosphatase epsilon is an enzyme that in humans is encoded by the PTPRE gene.
Receptor-type tyrosine-protein phosphatase mu is an enzyme that in humans is encoded by the PTPRM gene.
Receptor-type tyrosine-protein phosphatase S, also known as R-PTP-S, R-PTP-sigma, or PTPσ, is an enzyme that in humans is encoded by the PTPRS gene.
Proline-serine-threonine phosphatase-interacting protein 1 is an enzyme that in humans is encoded by the PSTPIP1 gene.
Metastasis suppressor protein 1 is a protein that in humans is encoded by the MTSS1 gene. True to its name, it codes for a metastasis suppressor.
Receptor-type tyrosine-protein phosphatase delta is an enzyme that, in humans, is encoded by the PTPRD gene.
Tyrosine-protein phosphatase non-receptor type 18 is an enzyme that in humans is encoded by the PTPN18 gene.
Tyrosine-protein phosphatase non-receptor type 21 is an enzyme that in humans is encoded by the PTPN21 gene.
Tensin was first identified as a 220 kDa multi-domain protein localized to the specialized regions of plasma membrane called integrin-mediated focal adhesions. Genome sequencing and comparison have revealed the existence of four tensin genes in humans. These genes appear to be related by ancient instances of gene duplication.