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Regulation
''' The Receptor Tyrosine Kinase (RTK) pathway is carefully regulated by a variety of positive and negative feedback loops. Because RTKs coordinate a wide variety of cellular functions such as cell proliferation and differentiation, they must be regulated to prevent severe abnormalities in cellular functioning such as cancer and fibrosis. (Fawaz et al).

Protein Tyrosine Phosphatases
Protein Tyrosine Phosphatase (PTPs) are a group of enzymes that possess a catalytic domain with phosphotyrosine-specific phosphohydrolase activity (Ostman et al). PTPs are capable of modifying the activity of receptor Tyrosine kinases in both a positive and negative manner. PTPs can dephosphorylate the activated phosphorylated tyrosine residues on the RTKs (Kovalenko et al, 2000) which virtually leads to termination of the signal. Studies involving PTP1B, a widely known PTP involved in the regulation of the cell cycle and cytokine receptor signaling, has shown to dephosphorylate the epidermal growth factor receptor (Flint et al 1997) and the insulin receptor (Kenner, et al 1996). Some PTPs, on the other hand, are cell surface receptors that play a positive role in cell signaling proliferation. Cd45, a cell surface glycoprotein, plays a critical role in antigen-stimulated dephosphorylation of specific phosphotyrosines that inhibit the Src pathway.

Herstatin
Herstatin, an autoinhibitor of the ErbB family, which binds to RTKs and blocks receptor dimerization and tyrosine phosphorylation. CHO cells transfected with herstatin resulted in reduced receptor oligomerization, clonal growth and receptor tyrosine phosphorylation in response to EGF.

Receptor Endocytosis
Activated RTKs can undergo endocytosis resulting in down regulation of the receptor and eventually the signaling cascade. The molecular mechanism involves the engulfing of the RTK by a clathrin-mediated endocytosis leading to intracellular degradation.

Drug Therapy
RTKs have become an attractive target for drug therapy due to their implication in a variety of cellular abnormalities such as cancer, degenerative diseases and cardiovascular diseases. The United States Food and Drug Administration (FDA) has approved several anti-cancer drugs caused by activated RTKs. Drugs have been developed to target the extracellular domain or the catalytic domain, thus inhibiting ligand binding, receptor oligomerization. Heceptin, a monoclonal antibody that is capable of binding to the extracellular domain of RTKs, has be used to treat HER2 overexpression in breast cancer.

+ Table adapted fro "Cell signalling by recptor-tyrosine kinases," by Lemmon and Schlessinger's, 2010. Cell, 141, p. 1117–1134.