Alternative titles; symbols
HGNC Approved Gene Symbol: PSTPIP2
Cytogenetic location: 18q21.1 Genomic coordinates (GRCh38): 18:45,983,536-46,072,260 (from NCBI)
Wu et al. (1998) cloned mouse Pstpip2. The deduced 334-amino acid protein contains a potential central coiled-coil domain and 2 putative sites for tyrosine phosphorylation. Pstpip2 shares a high degree of similarity with Pstpip1 (606347), a cytoskeletal protein. Database analysis revealed 2 splice variants of human PSTPIP2 that encode proteins with deletions in either the N- or C-terminal regions compared with full-length mouse Pstpip2. Northern blot analysis revealed Pstpip2 expression in all mouse tissues examined. Epitope-tagged Pstpip2 localized to actin-rich cortical and lamellipodial regions of transfected Chinese hamster ovary (CHO) cells. During cytokinesis, Pstpip2 remained associated with the cell cortex and did not relocalize to the actin-rich cleavage furrow.
Yeung et al. (1998) reported that mouse Pstpip2, which they called Mayp, contains a Fes (190030)/Cip4 (TRIP10; 604504) homology domain and a putative actin-binding domain. Western blot analysis detected strong Mayp expression in mouse macrophage cell lines and primary mouse macrophages, but little to no expression in other mouse cell lines or tissues. Mayp had an apparent molecular mass of 37 kD.
Liu et al. (2014) found that expression of PSTPIP2 was high in human cord blood mononuclear cells and mouse bone marrow cells.
Using immunoprecipitation and protein pull-down assays, Wu et al. (1998) showed that mouse Pstpip2 interacted with PEST-type protein tyrosine phosphatases (PTPs; see 600079). Pstpip2 also formed homooligomers, but it did not interact with Pstpip1. Pstpip2 was endogenously tyrosine phosphorylated at 2 sites, and Pstpip2 showed tyrosine autophosphorylation activity in vitro. Overexpression of Pstpip2 resulted in formation of extensive meshwork-like structures throughout the cell cortex and cytoplasm in CHO cells.
Yeung et al. (1998) found that treatment of BAC1.2F5 mouse macrophages with recombinant human colony-stimulating factor-1 (CSF1; 120420) caused rapid tyrosine phosphorylation of Mayp. Mayp immunoprecipitated with actin from BAC1.2F5 cells.
Liu et al. (2014) identified a GATA1 (305371)-binding site in intron 1 of the PSTPIP2 gene and found that binding of GATA1 to this site downregulated PSTPIP2 expression during phorbol ester- or thrombopoietin (THPO; 600044)-induced differentiation in human and mouse megakaryocytic cell lines. PSTPIP2 inhibited growth and differentiation by recruiting PTPs, activating LYN kinase (165120), and repressing ERK (see 601795) phosphorylation and activation. GATA1-dependent downregulation of PSTPIP2 permitted activation of the signaling cascade for megakaryocyte growth and differentiation.
Hartz (2014) mapped the PSTPIP2 gene to chromosome 18q21.1 based on an alignment of the PSTPIP2 gene (GenBank AA082133) with the genomic sequence (GRCh38).
The mouse Pstpip2 gene maps to chromosome 18 (Ferguson et al., 2006).
Byrd et al. (1991) identified a disorder in mice that had features similar to those described in chronic recurrent multifocal osteomyelitis (CRMO; 259680) by Giedion et al. (1972). The phenotype was first recognized in mice with tail kinks and deformities of the hindlimbs. Breeding analysis showed that the defect was determined by a single autosomal recessive mutation. RFLP analysis of a linkage backcross indicated that the cmo gene resided on mouse chromosome 18. As in humans, no known pathogen could be isolated from the lesions.
Ferguson et al. (2006) described the CRMO phenotype in the cmo mouse, which includes bone, cartilage, and skin inflammation of the extremities and ears. They identified an leu98-to-pro (L98P) mutation in the Pstpip2 gene and suggested that this may be the cause of the autoinflammatory phenotype.
Byrd, L., Grossmann, M., Potter, M., Shen-Ong, G. L. C. Chronic multifocal osteomyelitis, a new recessive mutation on chromosome 18 of the mouse. Genomics 11: 794-798, 1991. [PubMed: 1686018] [Full Text: https://doi.org/10.1016/0888-7543(91)90002-v]
Ferguson, P. J., Bing, X., Vasef, M. A., Ochoa, L. A., Mahgoub, A., Waldschmidt, T. J., Tygrett, L. T., Schlueter, A. J., El-Shanti, H. A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis. Bone 38: 41-47, 2006. [PubMed: 16122996] [Full Text: https://doi.org/10.1016/j.bone.2005.07.009]
Giedion, A., Holthusen, W., Masel, L. F., Vischer, D. Subacute and chronic 'symmetrical' osteomyelitis. Ann. Radiol. 15: 329-342, 1972. [PubMed: 4403064]
Hartz, P. A. Personal Communication. Baltimore, Md. 10/7/2014.
Liu, L., Wen, Q., Gong, R., Stankiewicz, M. J., Li, W., Guo, M., Li, L., Sun, X., Li, W., Crispino, J. D., Huang, Z. PSTPIP2 dysregulation contributes to aberrant terminal differentiation in GATA-1 deficient megakaryocytes by activating LYN. Cell Death Dis. 5: e988, 2014. Note: Electronic Article. [PubMed: 24407241] [Full Text: https://doi.org/10.1038/cddis.2013.512]
Wu, Y., Dowbenko, D., Lasky, L. A. PSTPIP 2, a second tyrosine phosphorylated, cytoskeletal-associated protein that binds a PEST-type protein-tyrosine phosphatase. J. Biol. Chem. 273: 30487-30496, 1998. [PubMed: 9804817] [Full Text: https://doi.org/10.1074/jbc.273.46.30487]
Yeung, Y.-G., Soldera, S., Stanley, E. R. A novel macrophage actin-associated protein (MAYP) is tyrosine-phosphorylated following colony stimulating factor-1 stimulation. J. Biol. Chem. 273: 30638-30642, 1998. [PubMed: 9804836] [Full Text: https://doi.org/10.1074/jbc.273.46.30638]