Cells 2014, 3(2), 304-330; doi:10.3390/cells3020304

Mechanisms of Activation of Receptor Tyrosine Kinases: Monomers or Dimers

Received: 6 March 2014; in revised form: 10 April 2014 / Accepted: 11 April 2014 / Published: 22 April 2014
(This article belongs to the Special Issue Receptor Tyrosine Kinases)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Receptor tyrosine kinases (RTKs) play essential roles in cellular processes, including metabolism, cell-cycle control, survival, proliferation, motility and differentiation. RTKs are all synthesized as single-pass transmembrane proteins and bind polypeptide ligands, mainly growth factors. It has long been thought that all RTKs, except for the insulin receptor (IR) family, are activated by ligand-induced dimerization of the receptors. An increasing number of diverse studies, however, indicate that RTKs, previously thought to exist as monomers, are present as pre-formed, yet inactive, dimers prior to ligand binding. The non-covalently associated dimeric structures are reminiscent of those of the IR family, which has a disulfide-linked dimeric structure. Furthermore, recent progress in structural studies has provided insight into the underpinnings of conformational changes during the activation of RTKs. In this review, I discuss two mutually exclusive models for the mechanisms of activation of the epidermal growth factor receptor, the neurotrophin receptor and IR families, based on these new insights.
Keywords: BDNF; cancer; dimerization; EGFR; IGF; ligand; NGF; phosphorylation; rotation/twist; transmembrane signaling; Trk
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MDPI and ACS Style

Maruyama, I.N. Mechanisms of Activation of Receptor Tyrosine Kinases: Monomers or Dimers. Cells 2014, 3, 304-330.

AMA Style

Maruyama IN. Mechanisms of Activation of Receptor Tyrosine Kinases: Monomers or Dimers. Cells. 2014; 3(2):304-330.

Chicago/Turabian Style

Maruyama, Ichiro N. 2014. "Mechanisms of Activation of Receptor Tyrosine Kinases: Monomers or Dimers." Cells 3, no. 2: 304-330.

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