1uef

Structural highlights

Function

[DOK1_MOUSE] DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK1 appears to be a negative regulator of the insulin signaling pathway. Modulates integrin activation by competing with talin for the same binding site on ITGB3 (By similarity). [RET_MOUSE] Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration.^{[1] [2]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Veiga-Fernandes H, Coles MC, Foster KE, Patel A, Williams A, Natarajan D, Barlow A, Pachnis V, Kioussis D. Tyrosine kinase receptor RET is a key regulator of Peyer's patch organogenesis. Nature. 2007 Mar 29;446(7135):547-51. Epub 2007 Feb 25. PMID:17322904 doi:http://dx.doi.org/10.1038/nature05597
2. ↑ Golden JP, Hoshi M, Nassar MA, Enomoto H, Wood JN, Milbrandt J, Gereau RW 4th, Johnson EM Jr, Jain S. RET signaling is required for survival and normal function of nonpeptidergic nociceptors. J Neurosci. 2010 Mar 17;30(11):3983-94. doi: 10.1523/JNEUROSCI.5930-09.2010. PMID:20237269 doi:http://dx.doi.org/10.1523/JNEUROSCI.5930-09.2010
3. ↑ Shi N, Ye S, Bartlam M, Yang M, Wu J, Liu Y, Sun F, Han X, Peng X, Qiang B, Yuan J, Rao Z. Structural basis for the specific recognition of RET by the Dok1 phosphotyrosine binding domain. J Biol Chem. 2004 Feb 6;279(6):4962-9. Epub 2003 Nov 7. PMID:14607833 doi:http://dx.doi.org/10.1074/jbc.M311030200