ROR1 , or transmembrane receptor protein tyrosine kinase ROR1 , is a protein of the receptor tyrosine kinase family, which is encoded in humans by the ROR1 gene .
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| , NTRKR1, dJ537F10.1, receptor tyrosine kinase-like orphan receptor 1, receptor tyrosine kinase like orphan receptor 1 | |||||||||||||
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Content
Gene and protein structure
The ROR1 gene encoding a protein with a length of 937 amino acid residues was cloned in 1992 [1] .
ROR1 consists of three extracellular domains (immunoglobulin-like motif, frizzled and KNG domains), the transmembrane part and the cytoplasmic kinase domain [2] . In addition to the full-sized form of the protein, it is known that there is a shortened form, which is the result of alternative splicing [3] . It is believed that the catalytic domain of ROR1 is non-functional, and thus, ROR1 is a pseudokinase [4] .
Distribution
ROR1 is synthesized in many embryonic tissues (predominates in the nervous ), but is practically not found in normal tissues of an adult organism [2] . Also, this protein is synthesized for a short time at an intermediate stage of development of B-lymphocytes [5] . In addition, abnormal ROR1 synthesis is found in malignant tumors (including blood tumors ) and correlates with poor chances of recovery [2] .
Functions
The functions of ROR1 in the body have not yet been fully studied. It is believed that it plays a large role in embryonic development . In one study, mice lacking the ROR1 gene had no visible developmental defects, but died soon after birth from respiratory dysfunction [6] . In another experiment, such mice survived, but had numerous abnormalities in the skeletal and urogenital systems and were characterized by slow development [7] .
ROR1 can play a special role in the development and maintenance of malignant tumors. For example, it has recently been found that ROR1 promotes the survival of tumor cells in certain types of acute lymphoblastic leukemia [8] .
Notes
- ↑ Masiakowski P., Carroll RD A novel family of cell surface receptors with tyrosine kinase-like domain // J Biol Chem .. - 1992.- T. 267 , no. 36 . - S. 26181—26190 . - PMID 1334494 .
- ↑ 1 2 3 Rebagay G., Yan S., Liu C., Cheung NK ROR1 and ROR2 in Human Malignancies: Potentials for Targeted Therapy // Front Oncol .. - 2012 .-- T. 2 . - S. 34 . - DOI : 10.3389 / fonc.2012.00034 . - PMID 22655270 .
- ↑ Reddy UR, Phatak S., Allen C., Nycum LM, Sulman EP, White PS, Biegel JA Localization of the human Ror1 gene (NTRKR1) to chromosome 1p31-p32 by fluorescence in situ hybridization and somatic cell hybrid analysis // Genomics . - 1997. - T. 41 , no. 2 . - S. 283-285 . - PMID 9143508 .
- ↑ Gentile A., Lazzari L., Benvenuti S., Trusolino L., Comoglio PM Ror1 is a pseudokinase that is crucial for Met-driven tumorigenesis // Cancer Res .. - 2011 .-- T. 71 , no. 8 . - S. 3132-31341 . - DOI : 10.1158 / 0008-5472.CAN-10-2662 . - PMID 21487037 .
- ↑ Hudecek M., Schmitt TM, Baskar S., Lupo-Stanghellini MT, Nishida T., Yamamoto TN, Bleakley M., Turtle CJ, Chang WC, Greisman HA, Wood B., Maloney DG, Jensen MC, Rader C. , Riddell SR The B-cell tumor-associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor // Blood. - 2010 .-- T. 116 , no. 22 . - S. 4532–4541 . - DOI : 10.1182 / blood-2010-05-283309 . - PMID 20702778 .
- ↑ Nomi M., Oishi., Kani S., Suzuki H., Matsuda T., Yoda A., Kitamura M., Itoh K., Takeuchi S., Takeda K., Akira S., Ikeya M., Takada S ., Minami Y. Loss of mRor1 enhances the heart and skeletal abnormalities in mRor2-deficient mice: redundant and pleiotropic functions of mRor1 and mRor2 receptor tyrosine kinases // Mol Cell Biol .. - 2001.- T. 21 , no. 24 . - S. 8329-8335 . - PMID 11713269 .
- ↑ Lyashenko N., Weissenböck M., Sharir A., Erben RG, Minami Y., Hartmann C. Mice lacking the orphan receptor ror1 have distinct skeletal abnormalities and are growth retarded // Dev Dyn .. - 2010.- T. 239 , issue 8 . - S. 2266-2277 . - DOI : 10.1002 / dvdy.22362 . - PMID 20593419 .
- ↑ Bicocca VT, Chang BH, Kharabi Masouleh B., Muschen M., Loriaux MM, Druker BJ, Tyner JW Crosstalk between ROR1 and the Pre-B Cell Receptor Promotes Survival of t (1; 19) Acute Lymphoblastic Leukemia // Cancer Cell . - 2012 .-- T. 22 , no. 5 . - S. 656-667 . - DOI : 10.1016 / j.ccr.2012.08.08.027 . - PMID 23153538 .