CN103160570A - Discovery for interaction mechanism of UNC-51 kinase and PP1 phosphatase - Google Patents
Discovery for interaction mechanism of UNC-51 kinase and PP1 phosphatase Download PDFInfo
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- CN103160570A CN103160570A CN2011104077691A CN201110407769A CN103160570A CN 103160570 A CN103160570 A CN 103160570A CN 2011104077691 A CN2011104077691 A CN 2011104077691A CN 201110407769 A CN201110407769 A CN 201110407769A CN 103160570 A CN103160570 A CN 103160570A
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- 101100316118 Caenorhabditis elegans unc-51 gene Proteins 0.000 title claims abstract description 28
- 108091000080 Phosphotransferase Proteins 0.000 title claims abstract description 20
- 102000020233 phosphotransferase Human genes 0.000 title claims abstract description 20
- 230000003993 interaction Effects 0.000 title abstract description 4
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 title abstract 4
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 title abstract 4
- 238000006366 phosphorylation reaction Methods 0.000 claims abstract description 17
- 230000026731 phosphorylation Effects 0.000 claims abstract description 12
- 230000030609 dephosphorylation Effects 0.000 claims abstract description 11
- 238000006209 dephosphorylation reaction Methods 0.000 claims abstract description 10
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 claims abstract description 6
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 claims abstract description 6
- 102000007469 Actins Human genes 0.000 claims abstract description 5
- 108010085238 Actins Proteins 0.000 claims abstract description 5
- 230000002860 competitive effect Effects 0.000 claims abstract description 5
- 210000003050 axon Anatomy 0.000 claims abstract description 4
- 238000012691 depolymerization reaction Methods 0.000 claims abstract description 4
- 230000000694 effects Effects 0.000 claims abstract description 4
- 210000003632 microfilament Anatomy 0.000 claims abstract description 4
- 210000004556 brain Anatomy 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 34
- 108010013043 Acetylesterase Proteins 0.000 claims description 17
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 17
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 6
- 102000004243 Tubulin Human genes 0.000 claims description 4
- 108090000704 Tubulin Proteins 0.000 claims description 4
- 210000003205 muscle Anatomy 0.000 claims description 4
- 230000001537 neural effect Effects 0.000 claims description 4
- 102000002151 Microfilament Proteins Human genes 0.000 claims description 3
- 108010040897 Microfilament Proteins Proteins 0.000 claims description 3
- 230000003834 intracellular effect Effects 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 210000004292 cytoskeleton Anatomy 0.000 abstract description 2
- 230000001939 inductive effect Effects 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 abstract description 2
- 102000004169 proteins and genes Human genes 0.000 abstract description 2
- 210000005036 nerve Anatomy 0.000 abstract 2
- 241000244203 Caenorhabditis elegans Species 0.000 abstract 1
- 102100030011 Endoribonuclease Human genes 0.000 abstract 1
- 101710199605 Endoribonuclease Proteins 0.000 abstract 1
- 102000029749 Microtubule Human genes 0.000 abstract 1
- 108091022875 Microtubule Proteins 0.000 abstract 1
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 abstract 1
- 230000005754 cellular signaling Effects 0.000 abstract 1
- 210000004688 microtubule Anatomy 0.000 abstract 1
- 210000003470 mitochondria Anatomy 0.000 abstract 1
- 230000004766 neurogenesis Effects 0.000 abstract 1
- 210000002569 neuron Anatomy 0.000 abstract 1
- 230000026683 transduction Effects 0.000 abstract 1
- 238000010361 transduction Methods 0.000 abstract 1
- 101150017998 unc-51 gene Proteins 0.000 abstract 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
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- Enzymes And Modification Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention discloses discovery for the interaction mechanism of UNC-51 kinase and PP1 phosphatase, wherein phosphorylation and dephosphorylation for proteins belong to one of the most important research fields of bioscience; serine/threonine protein kinase with conservation property in the evolution from nematoid to human is encoded by UNC-51 gene which is necessary to the neurogenesis of caenorhabditis elegans. The discovery disclosed by the invention shows for the first time that UNC-51 kinase can be bound with PP1 phosphatase, self-phosphorylation UNC-51 kinase can be dephosphorylated by PP1 phosphatase instead of PP2B phosphatase, and the microtubulins and the actins phosphorylated by UNC-51 kinase can also be dephosphorylated by PP1 phosphatase instead of PP2B phosphatase, and shows the new interaction mechanism of UNC-51 kinase and PP1 phosphatase. The discovery puts forward, for the first time, a model formed by inducing nerve axons via the competitive phosphorylation depolymerization reaction for microtubules and microfilaments in cells, mitochondrion conveying and the competitive synergy of the PP1 reverse reaction of the activity of the UNC-51 kinase. Via the discovery disclosed by the invention, important and new contents are added for many fields of basic life science, biochemistry, brain science, nerve cell signalling transduction science, nerve cytoskeleton science, and the like.
Description
Technical field:
The invention belongs to the Basic Life science, biological chemistry, brain science, a plurality of fields such as neurocyte signal transduction and neurocyte skeleton have been disclosed UNC-51 kinases and the interactional new mechanism of phosphoprotein phosphatase PP1 first.
Background technology:
Phosphorylation and dephosphorylation are one of most important research fields of life science.Having conservatory protein serine/threonine in evolution from the nematode to the mankind of the unc-51 genes encoding of C. Elegans Automatic Screening, is that neural formation is necessary.In fields such as neuroscience and cytoskeleton science, it is very important that announcement can make by the Phosphoric acid esterase of the protein dephosphorylation of UNC-51 tyrosine phosphorylation.
Summary of the invention:
The object of the invention is to disclose the Phosphoric acid esterase that can make by the protein dephosphorylation of UNC-51 tyrosine phosphorylation, understand the molecule mechanism that neurocyte forms, for the treatment of sacred disease provides brand-new principle and method.Content of the present invention is:
(1) disclose first UNC-51 kinases energy and the combination of PP1 Phosphoric acid esterase
As shown in Figure 1, the result of vitro enzyme linked immunosorbent assay shows, compares with contrast bovine serum albumin (BSA), and PP1 Phosphoric acid esterase and PP2B Phosphoric acid esterase can both be in conjunction with the UNC-51 kinase proteins.
(2) disclosing first self-phosphorylation UNC-51 kinases can be by PP1 Phosphoric acid esterase dephosphorylation, also can be by PP1 Phosphoric acid esterase dephosphorylation by the tubulin of UNC-51 tyrosine phosphorylation and Actin muscle
Fig. 2 shows that self-phosphorylation UNC-51 kinases can be by PP1 Phosphoric acid esterase dephosphorylation, also can be by PP1 Phosphoric acid esterase dephosphorylation by the tubulin of UNC-51 tyrosine phosphorylation and Actin muscle; And the PP2B Phosphoric acid esterase can not.
Fig. 3 represents the UNC-51 kinase activity by to the competitive phosphorylation depolymerization reaction of intracellular canaliculus and microfilament, plastosome carry with and the competition of PP1 reversed reaction work in coordination with the model of inducing neural axon to form.
Description of drawings:
The external combination of Fig. 1 UNC-51 kinases and PP1 Phosphoric acid esterase
Fig. 2 PP1 Phosphoric acid esterase makes by the tubulin of UNC-51 tyrosine phosphorylation external, the UNC-51 kinases dephosphorylation of Actin muscle and self-phosphorylation
The model of Fig. 3 UNC-51 kinase activity by the competition of the dephosphorylation reaction of the competitive phosphorylation depolymerization reaction of intracellular canaliculus and microfilament and PP1 Phosphoric acid esterase thereof being worked in coordination with induce neural axon to form
Claims (3)
- The present invention has found UNC-51 kinases and the interactional new mechanism of phosphoprotein phosphatase PP1 first.Its key is found to be:1. disclose first UNC-51 kinases energy and the combination of PP1 Phosphoric acid esterase.
- 2. disclosing first self-phosphorylation UNC-51 kinases can be by PP1 Phosphoric acid esterase dephosphorylation, also can be by PP1 Phosphoric acid esterase dephosphorylation by the tubulin of UNC-51 tyrosine phosphorylation and Actin muscle, the UNC-51 kinase activity is by to the competitive phosphorylation depolymerization reaction of intracellular canaliculus and microfilament, plastosome carry with and the competition of PP1 reversed reaction work in coordination with to induce neural axon to form.
- 3. remember the know-why of binomial requirement in life science, brain science, tumour science, computer science, space science, traffic science, medical science, pharmacy and pharmacopedics, the Chinese medicine science, the therapeutics of various diseases, the application of medical skill and every other aspect and popularization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104077691A CN103160570A (en) | 2011-12-09 | 2011-12-09 | Discovery for interaction mechanism of UNC-51 kinase and PP1 phosphatase |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104077691A CN103160570A (en) | 2011-12-09 | 2011-12-09 | Discovery for interaction mechanism of UNC-51 kinase and PP1 phosphatase |
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| Publication Number | Publication Date |
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| CN103160570A true CN103160570A (en) | 2013-06-19 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011104077691A Pending CN103160570A (en) | 2011-12-09 | 2011-12-09 | Discovery for interaction mechanism of UNC-51 kinase and PP1 phosphatase |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105548301A (en) * | 2016-01-28 | 2016-05-04 | 中南大学 | Method for measuring activity of protein kinase and method for measuring activity of protein kinase inhibitor |
| CN112654700A (en) * | 2018-07-06 | 2021-04-13 | 科罗拉多州立大学董事会法人团体 | Gene coding systems for the construction and detection of biologically active agents |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002079478A2 (en) * | 2001-03-30 | 2002-10-10 | DeveloGen Aktiengesellschaft für entwicklungsbiologische Forschung | Modification of organelle metabolism by a composition comprising unc-51-like kinases, roma1, or 2tm polypeptides and uses thereof for the preration of a medicament for the treatment disorders |
| CN101104615A (en) * | 2006-07-13 | 2008-01-16 | 陈正书 | Anticancer cytoskeleton inhibiting and cell elongation inducing compound and synthesis method thereof |
| CN102083443A (en) * | 2008-04-09 | 2011-06-01 | 北卡罗来纳大学查珀尔希尔分校 | Methods of regulating actin cytoskeletal rearrangement and intercellular gap formation |
-
2011
- 2011-12-09 CN CN2011104077691A patent/CN103160570A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002079478A2 (en) * | 2001-03-30 | 2002-10-10 | DeveloGen Aktiengesellschaft für entwicklungsbiologische Forschung | Modification of organelle metabolism by a composition comprising unc-51-like kinases, roma1, or 2tm polypeptides and uses thereof for the preration of a medicament for the treatment disorders |
| CN101104615A (en) * | 2006-07-13 | 2008-01-16 | 陈正书 | Anticancer cytoskeleton inhibiting and cell elongation inducing compound and synthesis method thereof |
| CN102083443A (en) * | 2008-04-09 | 2011-06-01 | 北卡罗来纳大学查珀尔希尔分校 | Methods of regulating actin cytoskeletal rearrangement and intercellular gap formation |
Non-Patent Citations (1)
| Title |
|---|
| HUAIZE TIAN ET AL.: "Protein Phosphate 1α Reverse UNC-51 Phosphorylations of Both Actins and Tubulins and a New Model of UNC-51-Inducing Axon Formation", 《ANIMAL CELL TECHNOLOGY: BASIC & APPLIED ASPECTS》, vol. 15, 31 December 2009 (2009-12-31) * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105548301A (en) * | 2016-01-28 | 2016-05-04 | 中南大学 | Method for measuring activity of protein kinase and method for measuring activity of protein kinase inhibitor |
| CN105548301B (en) * | 2016-01-28 | 2018-07-31 | 中南大学 | A kind of method and the active method of kinases inhibitor measuring protein kinase activity |
| CN112654700A (en) * | 2018-07-06 | 2021-04-13 | 科罗拉多州立大学董事会法人团体 | Gene coding systems for the construction and detection of biologically active agents |
| US11472847B2 (en) | 2018-07-06 | 2022-10-18 | The Regents Of The University Of Colorado | Genetically encoded system for constructing and detecting biologically active agents |
| CN112654700B (en) * | 2018-07-06 | 2023-06-16 | 科罗拉多州立大学董事会法人团体 | Gene coding system for constructing and detecting bioactive agents |
| US11993635B2 (en) | 2018-07-06 | 2024-05-28 | The Regents Of The University Of Colorado, A Body Corporate | Genetically encoded system for constructing and detecting biologically active agents |
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Application publication date: 20130619 |