Is ALK a proto oncogene?

Anaplastic lymphoma kinase (ALK) and leukocyte tyrosine kinase (LTK), are two well-known RTK proto-oncogenes whose roles in oncogenesis and potential as therapeutic targets have been intensively studied (9, 14–22).

Is ALK a receptor tyrosine kinase?

The anaplastic lymphoma kinase (ALK) receptor is a membrane-bound tyrosine kinase. The pathogenesis of several cancers is closely related to aberrant forms of ALK or aberrant ALK expression, including ALK fusion proteins, ALK-activated point mutations, and ALK amplification.

How is tyrosine kinase activated?

Tyrosine kinases are enzymes that selectively phosphorylates tyrosine residue in different substrates. Receptor tyrosine kinases are activated by ligand binding to their extracellular domain. Ligands are extracellular signal molecules (e.g. EGF, PDGF etc) that induce receptor dimerization (except Insulin receptor).

What type of gene is ALK?

ALK (ALK Receptor Tyrosine Kinase) is a Protein Coding gene. Diseases associated with ALK include Neuroblastoma 3 and Neuroblastoma. Among its related pathways are GPCR Pathway and Crizotinib Pathway, Pharmacokinetics/Pharmacodynamics.

What is ALK test?

ALK is a short name for the anaplastic lymphoma receptor tyrosine kinase gene. This test detects specific rearrangements in the ALK gene in cancer cells and tissue. The presence of these changes makes it more likely that a person with non-small cell lung cancer will respond to a targeted drug therapy.

How is ALK activated?

ALK becomes activated only upon ligand-induced homo-dimerization, and inactivated through de-phosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) in the absence of the ligand [7].

What is the function of ALK?

Normal Function The ALK gene provides instructions for making a protein called ALK receptor tyrosine kinase, which is part of a family of proteins called receptor tyrosine kinases (RTKs). Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction.

What do tyrosine kinase receptors do when activated?

In particular, the binding of a signaling molecule with an RTK activates tyrosine kinase in the cytoplasmic tail of the receptor. This activity then launches a series of enzymatic reactions that carry the signal to the nucleus, where it alters patterns of protein transcription.

How do you activate kinase?

For many kinases, activation requires phosphorylation of the activation segment, a region of the protein that has become a major focus for understanding the relationship between structure and function in protein kinases.

What is ALK test for?

Is ALK-positive curable?

As these cancer cells begin to grow in your lung, they can potentially spread to other parts of your body. Among the many different mutations that can drive cancer to grow, the ALK mutation is one of the more treatable as it often responds dramatically to targeted therapy.

What causes the ALK mutation?

ALK is short for anaplastic lymphoma kinase. It’s a mutation in the DNA of your lung cells that happens when two genes become fused, or stuck together. When you have this mutation, your lung cells make too many copies of themselves.

How is the ALK gene related to the LTK gene?

Cited for: REVIEW ON FUNCTION. “ALK, the chromosome 2 gene locus altered by the t (2;5) in non-Hodgkin’s lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK).”

What are the tyrosine kinase precursors of ALK?

Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction.

How is the ALK receptor used in cancer treatment?

This review summarises the latest research on the receptor tyrosine kinase ALK, and how this information can guide the management of patients with cancer that is ALK-positive. A variety of ALK gene alterations have been described across a range of tumour types, including point mutations, deletions and rearrangements.

How does MDK bind to the ALK receptor?

Functioni. 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. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase.