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).
May function as regulator of gastric epithelial differentiation (By similarity)
Homodimer; homodimerizes following heparin- and ligand-binding (PubMed:16317043, PubMed:25605972, PubMed:34646012, PubMed:34819673). Interacts with CBL, IRS1, PIK3R1 and PLCG1 (PubMed:15226403). Interacts with FRS2 and SHC1 (PubMed:15226403, PubMed:16878150, PubMed:17274988).
Interacts with PTN and MDK (PubMed:11278720, PubMed:12122009)
Expressed in brain and CNS. Also expressed in the small intestine and testis, but not in normal lymphoid cells
The EGF-like region drives the cytokine specificity for ALKAL2
The heparin-binding region binds heparin glycosaminoglycan (PubMed:25605972, PubMed:34646012). Heparin-binding is required for ALKAL2-driven activation (PubMed:34646012)
A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system.
| Cancer Type | Mutation Percentage |
|---|---|
| Central Nervous System Astrocytoma Grade Iv | 0.38% |
| Lung Adenocarcinoma | 4.28% |
| Lung Small Cell Carcinoma | 3.56% |
| Lung Squamous Cell Carcinoma | 2.86% |
| Oesophagus Adenocarcinoma | 6.19% |
| Oesophagus Squamous Cell Carcinoma | 1.41% |
| Pancreas Ductal Carcinoma | 1.38% |
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to ALK, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 428
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT06074588 | Non-small Cell Lung Cancer (NSCLC) | Sacituzumab Tirumotecan (MK-2870) Versus Chemotherapy in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations (MK-2870-004) | PHASE3 | RECRUITING |
| NCT06234579 | ALK Gene Mutation, NSCLC Stage IV, ALK Sensitizing Mutation | Longitudinal Assessment of Genomic Alterations and Clonal Evolution in ALK-positive NSCLC (Galileo Project) | N/A | RECRUITING |
| NCT05991895 | Non-small Cell Lung Cancer (NSCLC) | Real-World Study of Iruplinalkib in the Treatment of ALK-Positive Non-Small Cell Lung Cancer | N/A | RECRUITING |
| NCT00907920 | Neuroblastoma | Studying Tumor Samples From Young Patients With Neuroblastoma | N/A | COMPLETED |
| NCT03038672 | ALK-Positive Large B-Cell Lymphoma, Diffuse Large B-Cell Lymphoma Activated B-Cell Type, Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation, Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, EBV-Positive Mucocutaneous Ulcer, HHV8-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, High Grade B-Cell Lymphoma, Not Otherwise Specified, Intravascular Large B-Cell Lymphoma, Large B-Cell Lymphoma With 11q Aberration, Large B-Cell Lymphoma With IRF4 Rearrangement, Plasmablastic Lymphoma, Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System, Primary Effusion Lymphoma, Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Burkitt Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Gray-Zone Lymphoma, Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Recurrent Lymphomatoid Granulomatosis, Recurrent Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Recurrent Primary Mediastinal Large B-Cell Lymphoma, Recurrent T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Refractory Burkitt Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Refractory Gray-Zone Lymphoma, Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Refractory Primary Mediastinal Large B-Cell Lymphoma, Refractory T-Cell/Histiocyte-Rich Large B-Cell Lymphoma | Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas | PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT05765877 | Non-Small Cell Lung Cancer(NSCLC) | Neoadjuvant WX-0593 in Resectable ALK-positive or ROS1-positive Non-small Cell Lung Cancer | PHASE2 | RECRUITING |
| NCT04887519 | Carcinoma, Non-Small-Cell Lung, Anaplastic Lymphoma Kinase | A Study of Brigatinib to Treat Adults With Anaplastic Lymphoma Kinase (ALK) Positive Metastatic Non Small Cell Lung Cancer (NSCLC) | N/A | COMPLETED |
| NCT05055232 | ROS1 Rearrangement Non-small Cell Lung Cancer, ALK Rearrangement Non-small Cell Lung Cancer | A Phase I Study of XZP-3621 in Chinese Patients With ALK or ROS1 Rearrangement Non-small Cell Lung Cancer | PHASE1 | COMPLETED |
| NCT06834373 | Large B-Cell Lymphoma With IRF4 Rearrangement, Recurrent Aggressive B-Cell Non-Hodgkin Lymphoma, Recurrent ALK-Positive Large B-Cell Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type, Recurrent Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation, Recurrent Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Recurrent EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Recurrent Grade 3b Follicular Lymphoma, Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements, Recurrent High Grade B-Cell Lymphoma, Not Otherwise Specified, Recurrent Intravascular Large B-Cell Lymphoma, Recurrent Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Recurrent Primary Mediastinal Large B-Cell Lymphoma, Recurrent T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, Recurrent Transformed Non-Hodgkin Lymphoma, Refractory Aggressive B-Cell Non-Hodgkin Lymphoma, Refractory ALK-Positive Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type, Refractory Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation, Refractory Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Refractory EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Refractory Grade 3b Follicular Lymphoma, Refractory High Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements, Refractory High Grade B-Cell Lymphoma, Not Otherwise Specified, Refractory Intravascular Large B-Cell Lymphoma, Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Refractory Primary Mediastinal Large B-Cell Lymphoma, Refractory T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, Refractory Transformed Non-Hodgkin Lymphoma | Golcadomide and Rituximab as Bridging Therapy for Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma Before CAR T-cell Therapy | PHASE2 | RECRUITING |
| NCT03607188 | Non-small Cell Lung Cancer | Study of Alkotinib in Patients With Advanced Non Small Cell Lung Cancer | PHASE1 | COMPLETED |