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| Description | PTPD1 is a protein of 130 kDa composed 1174 amino acids.
It is constituted by an N-terminal sequence homologous to the Four-point-one Ezrin-Radixin-Moesin (FERM domain) protein family; a C-terminal catalytic domain (PTP) with the essential cysteine residue at position 1108; two putative SH3 domain binding domains (residues 565-574 and 334-343); an acidic region in the residues 712-722; two highly conserved SH2 binding motifs (Y158ESQ and Y217GEE) within the FERm domain that mediate interaction with src tyrosine kinase. |
| Expression | PTPD1 is widely expressed in a variety of tissues including placenta, lung, kidney, colon, skeletal muscle, and in most cell lines (HEK293, fibroblast, MCF-7; T82; B16). |
| Localisation | PTPD1 localizes at the outer mitochondrial membrane, the plasma membrane, Golgi apparatus, endoplasmic reticulum, actin filaments and adhesion plaques. |
| Function | PTPD1 is member of non-receptor tyrosine phosphatases that binds to- and activates src tyrosine kinase. PTPD1/src complex up-regulates epidermal growth factor receptor (EGFR) phosphorylation and increases ERK 1 / ERK 2 signaling in response to EGF. PTPD1 forms a stable complex with actin, src tyrosine kinase and FAK (Focal Adhesion Kinase). PTPD1 regulates FAK signalling and actin cytoskeleton remodelling, and promotes cell scattering and migration. Mitochondrial PTPD1 in complex with AKAP121 and src is required for efficient maintenance of mitochondrial membrane potential and oxidative ATP synthesis. PTPD1 has been also implicated in the regulation of the Tec family kinases and activation of Stat3 signaling pathway.
PTPD1 Interactors: KIF1C kinesin family member 1C, BMX non-receptor tyrosine kinase, Src v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian), TEC tyrosine kinase implicated in the signaling pathways of hematopoietic and antigen receptors, FAK tyrosine kinase of focal adhesion, Actin filaments |
| Homology | PTPD1 belongs to the same family of tyrosine phosphatase PTPH1 and PTPMEG1. |
| Mitochondrial AKAP121 binds and targets protein tyrosine phosphatase D1, a novel positive regulator of src signaling. |
| Cardone L, Carlucci A, Affaitati A, Livigni A, DeCristofaro T, Garbi C, Varrone S, Ullrich A, Gottesman ME, Avvedimento EV, Feliciello A |
| Molecular and cellular biology. 2004 ; 24 (11) : 4613-4626. |
| PMID 15143158 |
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| Protein-tyrosine Phosphatase PTPD1 Regulates Focal Adhesion Kinase Autophosphorylation and Cell Migration. |
| Carlucci A, Gedressi C, Lignitto L, Nezi L, Villa-Moruzzi E, Avvedimento EV, Gottesman M, Garbi C, Feliciello A |
| The Journal of biological chemistry. 2008 ; 283 (16) : 10919-10929. |
| PMID 18223254 |
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| Characterization of KIF1C, a new kinesin-like protein involved in vesicle transport from the Golgi apparatus to the endoplasmic reticulum. |
| Dorner C, Ciossek T, Müller S, M&oring;ller PH, Ullrich A, Lammers R |
| The Journal of biological chemistry. 1998 ; 273 (32) : 20267-20275. |
| PMID 9685376 |
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| Gene expression differences between the microsatellite instability (MIN) and chromosomal instability (CIN) phenotypes in colorectal cancer revealed by high-density cDNA array hybridization. |
| Dunican DS, McWilliam P, Tighe O, Parle-McDermott A, Croke DT |
| Oncogene. 2002 ; 21 (20) : 3253-3257. |
| PMID 12082642 |
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| Protein-tyrosine phosphatase D1, a potential regulator and effector for Tec family kinases. |
| Jui HY, Tseng RJ, Wen X, Fang HI, Huang LM, Chen KY, Kung HJ, Ann DK, Shih HM |
| The Journal of biological chemistry. 2000 ; 275 (52) : 41124-41132. |
| PMID 11013262 |
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| Identification of a novel protein tyrosine phosphatase with sequence homology to the cytoskeletal proteins of the band 4.1 family. |
| L'Abbé D, Banville D, Tong Y, Stocco R, Masson S, Ma S, Fantus G, Shen SH |
| FEBS letters. 1994 ; 356 (2-3) : 351-356. |
| PMID 7805871 |
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| Mitochondrial AKAP121 links cAMP and src signaling to oxidative metabolism. |
| Livigni A, Scorziello A, Agnese S, Adornetto A, Carlucci A, Garbi C, Castaldo I, Annunziato L, Avvedimento EV, Feliciello A |
| Molecular biology of the cell. 2006 ; 17 (1) : 263-271. |
| PMID 16251349 |
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| Src kinase associates with a member of a distinct subfamily of protein-tyrosine phosphatases containing an ezrin-like domain. |
| M&oring;ller NP, M&oring;ller KB, Lammers R, Kharitonenkov A, Sures I, Ullrich A |
| Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (16) : 7477-7481. |
| PMID 7519780 |
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