Recombinant human ALK protein (Active) is a Human Fragment protein, in the 1060 to 1620 aa range, expressed in Baculovirus infected Sf9, with >75% purity and suitable for SDS-PAGE, WB, FuncS.
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- Nature cancer 3:1211-12272022Targeting the ALK-CDK9-Tyr19 kinase cascade sensitizes ovarian and breast tumors to PARP inhibition via destabilization of the P-TEFb complex.Applications:Unspecified applicationReactive species:Unspecified reactive speciesYu-Yi Chu,Mei-Kuang Chen,Yongkun Wei,Heng-Huan Lee,Weiya Xia,Ying-Nai Wang,Clinton Yam,Jennifer L Hsu,Hung-Ling Wang,Wei-Chao Chang,Hirohito Yamaguchi,Zhou Jiang,Chunxiao Liu,Ching-Fei Li,Lei Nie,Li-Chuan Chan,Yuan Gao,Shao-Chun Wang,Jinsong Liu,Shannon N Westin,Sanghoon Lee,Anil K Sood,Liuqing Yang,Gabriel N Hortobagyi,Dihua Yu,Mien-Chie HungPubMed 36253486
Key facts
- Purity
- >75% Densitometry
- Expression system
- Baculovirus infected Sf9 cells
- Tags
- GST tag N-Terminus
- Applications
- SDS-PAGE, WB, FuncS
- Biologically active
- Yes
Amino acid sequence
R R K H Q E L Q A M Q M E L Q S P E Y K L S K L R T S T I M T D Y N P N Y C F A G K T S S I S D L K E V P R K N I T L I R G L G H G A F G E V Y E G Q V S G M P N D P S P L Q V A V K T L P E V C S E Q D E L D F L M E A L I I S K F N H Q N I V R C I G V S L Q S L P R F I L L E L M A G G D L K S F L R E T R P R P S Q P S S L A M L D L L H V A R D I A C G C Q Y L E E N H F I H R D I A A R N C L L T C P G P G R V A K I G D F G M A R D I Y R A S Y Y R K G G C A M L P V K W M P P E A F M E G I F T S K T D T W S F G V L L W E I F S L G Y M P Y P S K S N Q E V L E F V T S G G R M D P P K N C P G P V Y R I M T Q C W Q H Q P E D R P N F A I I L E R I E Y C T Q D P D V I N T A L P I E Y G P L V E E E E K V P V R P K D P E G V P P L L V S Q Q A K R E E E R S P A A P P P L P T T S S G K A A K K P T A A E I S V R V P R G P A V E G G H V N M A F S Q S N P P S E L H K V H G S R N K P T S L W N P T Y G S W F T E K P T K K N N P I A K K E P H D R G N L G L E G S C T V P P N V A T G R L P G A S L L L E P S S L T A N M K E V P L F R L R H F P C G N V N Y G Y Q Q Q G L P L E A A T A P G A G H Y E D T I L K S K N S M N Q P G P
Reactivity data
| Application | Reactivity | Dilution info | Notes |
|---|---|---|---|
Application SDS-PAGE | Reactivity Reacts | Dilution info - | Notes - |
Application WB | Reactivity Reacts | Dilution info - | Notes - |
Application FuncS | Reactivity Reacts | Dilution info - | Notes - |
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Target data
Function
Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150).
Alternative names
CD246, ALK tyrosine kinase receptor, Anaplastic lymphoma kinase, ALK
Recommended products
Recombinant human ALK protein (Active) is a Human Fragment protein, in the 1060 to 1620 aa range, expressed in Baculovirus infected Sf9, with >75% purity and suitable for SDS-PAGE, WB, FuncS.
Key facts
- Purity
- >75% Densitometry
- Expression system
- Baculovirus infected Sf9 cells
- Tags
- GST tag N-Terminus
- Applications
- SDS-PAGE, WB, FuncS
- Biologically active
- Yes
- Biological activity
- The specific activity of ab187246 was determined to be 24 nmol/min/mg.
- Accession
- Q9UM73-1
- Animal free
- No
- Species
- Human
- Concentration
- Storage buffer
pH: 7.5
Preservative: 1.02% Imidazole
Constituents: 25% Glycerol (glycerin, glycerine), 1.75% Sodium chloride, 0.71% Sodium phosphate, 0.004% (R*,R*)-1,4-Dimercaptobutan-2,3-diol, 0.002% PMSF
Sequence info
Amino acid sequence
- R R K H Q E L Q A M Q M E L Q S P E Y K L S K L R T S T I M T D Y N P N Y C F A G K T S S I S D L K E V P R K N I T L I R G L G H G A F G E V Y E G Q V S G M P N D P S P L Q V A V K T L P E V C S E Q D E L D F L M E A L I I S K F N H Q N I V R C I G V S L Q S L P R F I L L E L M A G G D L K S F L R E T R P R P S Q P S S L A M L D L L H V A R D I A C G C Q Y L E E N H F I H R D I A A R N C L L T C P G P G R V A K I G D F G M A R D I Y R A S Y Y R K G G C A M L P V K W M P P E A F M E G I F T S K T D T W S F G V L L W E I F S L G Y M P Y P S K S N Q E V L E F V T S G G R M D P P K N C P G P V Y R I M T Q C W Q H Q P E D R P N F A I I L E R I E Y C T Q D P D V I N T A L P I E Y G P L V E E E E K V P V R P K D P E G V P P L L V S Q Q A K R E E E R S P A A P P P L P T T S S G K A A K K P T A A E I S V R V P R G P A V E G G H V N M A F S Q S N P P S E L H K V H G S R N K P T S L W N P T Y G S W F T E K P T K K N N P I A K K E P H D R G N L G L E G S C T V P P N V A T G R L P G A S L L L E P S S L T A N M K E V P L F R L R H F P C G N V N Y G Y Q Q Q G L P L E A A T A P G A G H Y E D T I L K S K N S M N Q P G P
- Accession
- Q9UM73
- Protein length
- Fragment
- Predicted molecular weight
- 90 kDa
- Amino acids
- 1060 to 1620
- Nature
- Recombinant
- Tags
- GST tag N-Terminus
Specifications
- Form
- Liquid
- Additional notes
Affinity purified.
General info
- Function
Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150).
- Sequence similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
- Post-translational modifications
Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity (PubMed:11121404, PubMed:15938644, PubMed:16878150, PubMed:34819673). In cells not stimulated by a ligand, receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) dephosphorylates ALK at the sites in ALK that are undergoing autophosphorylation through autoactivation (PubMed:17681947). Phosphorylation at Tyr-1507 is critical for SHC1 association (PubMed:17274988).
Storage
- Shipped at conditions
- Dry Ice
- Appropriate short-term storage conditions
- -80°C
- Appropriate long-term storage conditions
- -80°C
- Aliquoting information
- Upon delivery aliquot
- Storage information
- Avoid freeze / thaw cycle
This product is an active protein and may elicit a biological response in vivo, handle with caution.
Notes
IRS1 peptide ab204862 (IRS1 peptide) can be utilized as a substrate for assessing kinase activity.
Endogenous insect GST binding proteins are found in the final product. The final product is not purified from these contaminants (~26 kDa) as they do not affect the function and activity of the recombinant protein.
Supplementary info
- This supplementary information is collated from multiple sources and compiled automatically.
- Activity summary
The Anaplastic Lymphoma Kinase commonly referred to as ALK is a receptor tyrosine kinase known for its role in cell signaling. It is sometimes called CD246. ALK has a molecular mass of approximately 180 kDa. This protein finds expression predominantly in the central and peripheral nervous system with prominence in neural tissue during development. The ALK protein belongs to the insulin receptor superfamily exhibiting kinase activity that promotes signal transduction processes associated with growth and differentiation.
- Biological function summary
ALK influences cell growth survival and differentiation playing a significant role during the development of the nervous system. As part of its biological activity the ALK protein can become a component of larger signaling complexes participating as an important activator or mediator. Evidence suggests ALK's involvement in neuronal differentiation and synaptogenesis. Its activity impacts intracellular pathways consequently modulating biological processes relevant to neural tissue and oncogenesis.
- Pathways
ALK acts within the MAPK and PI3K-AKT signaling pathways. These pathways enable the transduction of signals from the cell surface to the nucleus influencing cellular outcomes such as proliferation and survival. In these pathways ALK interacts with various other proteins including GRB2 and PI3K which further facilitate downstream signaling. Proper functioning of these pathways is essential to maintaining cellular homeostasis and development.
- Associated diseases and disorders
ALK has a significant relationship with certain types of cancer such as non-small cell lung carcinoma and anaplastic large cell lymphoma. Genetic alterations in ALK such as translocations or mutations can lead to the uncontrolled activation of its kinase activity resulting in oncogenic transformation. In these contexts the ALK protein often interacts with EML4 in lung cancer through a fusion forming an oncogenic driver. Targeting ALK with anti-ALK antibodies or small molecule inhibitors has emerged as a therapeutic strategy to manage these malignancies.
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4 product images
Functional Studies - Recombinant human ALK protein (Active) (ab187246)
The specific activity of ALK (ab187246) was determined to be 24.4 nmol/min/mg as per activity assay protocol
SDS-PAGE - Recombinant human ALK protein (Active) (ab187246)
SDS PAGE analysis of ab187246
Functional Studies - Recombinant human ALK protein (Active) (ab187246)
Kinase assay showing the specific activity of ab187246 as 24 nmol/min/mg.
SDS-PAGE - Recombinant human ALK protein (Active) (ab187246)
SDS-PAGE analysis of ab187246.
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