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2013 ; 5
(10
): a008979
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Receptor tyrosine kinases in the nucleus
#MMPMID24086039
Carpenter G
; Liao HJ
Cold Spring Harb Perspect Biol
2013[Oct]; 5
(10
): a008979
PMID24086039
show ga
To date, 18 distinct receptor tyrosine kinases (RTKs) are reported to be
trafficked from the cell surface to the nucleus in response to ligand binding or
heterologous agonist exposure. In most cases, an intracellular domain (ICD)
fragment of the receptor is generated at the cell surface and translocated to the
nucleus, whereas for a few others the intact receptor is translocated to the
nucleus. ICD fragments are generated by several mechanisms, including
proteolysis, internal translation initiation, and messenger RNA (mRNA) splicing.
The most prevalent mechanism is intramembrane cleavage by ?-secretase. In some
cases, more than one mechanism has been reported for the nuclear localization of
a specific RTK. The generation and use of RTK ICD fragments to directly
communicate with the nucleus and influence gene expression parallels the
production of ICD fragments by a number of non-RTK cell-surface molecules that
also influence cell proliferation. This review will be focused on the individual
RTKs and to a lesser extent on other growth-related cell-surface transmembrane
proteins.
|*Models, Biological
[MESH]
|Active Transport, Cell Nucleus
[MESH]
|Amyloid Precursor Protein Secretases/metabolism/physiology
[MESH]
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