Signaling of Receptor Tyrosine Kinases in the Nucleus

Stephenson, Sally‐Anne; Mertens‐Walker, Inga; Herington, Adrian C.

doi:10.5772/36023

Cited by 5 publications

(7 citation statements)

References 131 publications

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“…To date, of the 58 reported human receptor tyrosine kinases, 18 have been found within the nucleus [36]. This includes another member of the Eph family, EphA4, which was found in the nuclei of the SaOS-2 osteoblastic cancer cell line, however the mechanism by which EphA4 translocates to the nucleus remains to be determined [37].…”

Section: Discussionmentioning

confidence: 99%

EphB4 localises to the nucleus of prostate cancer cells

Mertens‐Walker

Lisle

Nyberg

et al. 2015

Experimental Cell Research

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Section: Discussionmentioning

confidence: 99%

EphB4 localises to the nucleus of prostate cancer cells

Mertens‐Walker

Lisle

Nyberg

et al. 2015

Experimental Cell Research

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“…Interestingly, this cleavage event appears to precede a second cleavage event catalysed by the presenilin-dependent protease γ-secretase, which releases the intracellular part of EphB4 from the membrane. This mechanism -ectodomain shedding followed by release of an intracellular fragment, is common to many receptor tyrosine kinases and in many cases the released fragments have important biological functions (Stephenson et al, 2012). The biological consequences of these two EphB4 cleavage events, and the functions of the released fragments, are currently being explored in clinical prostate cancer samples and cell lines.…”

Section: Ephb4 and Its Ligand Ephrin-b2mentioning

confidence: 99%

Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases

Dong¹,

Harrington²,

Adams³

et al. 2014

Biological Chemistry

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The 15 members of the kallikrein-related serine peptidase (KLK) family have diverse tissue-specific expression profiles and roles in a range of cellular processes, including proliferation, migration, invasion, differentiation, inflammation and angiogenesis that are required in both normal physiology as well as pathological conditions. These roles require cleavage of a range of substrates, including extracellular matrix proteins, growth factors, cytokines as well as other proteinases. In addition, it has been clear since the earliest days of KLK research that cleavage of cell surface substrates is also essential in a range of KLK-mediated cellular processes where these peptidases are essentially acting as agonists and antagonists. In this review we focus on these KLK-regulated cell surface receptor systems including bradykinin receptors, proteinase-activated receptors, as well as the plasminogen activator, ephrins and their receptors, and hepatocyte growth factor/Met receptor systems and other plasma membrane proteins. From this analysis it is clear that in many physiological and pathological settings KLKs have the potential to regulate multiple receptor systems simultaneously; an important issue when these peptidases and substrates are targeted in disease.

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“…Following activation, RTKs are often endocytosed and trafficked to lysosomes for degradation or recycled and sent back to the cell surface ( Sorkin and Von Zastrow, 2002 ). In addition to this canonical role, in some contexts RTKs can participate in intracellular signaling from organelles such as the mitochondria and the nucleus ( Lin et al, 2001 ; Ni et al, 2001 ; Stephenson et al, 2012 ; Huo et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

“…Of the RTKs which have been observed in the nucleus, the ErbB family are the best characterized. ErbB1, ErbB2, and ErbB3 have all been detected in the nucleus as full-length polypeptides and are associated with increased proliferation and decreased sensitivity to growth-inhibitory signals ( Lo et al, 2005 ; Wang and Hung, 2009 ; Stephenson et al, 2012 ). ErbB4, on the other hand, is associated with growth suppression and better prognosis.…”

Section: Introductionmentioning

confidence: 99%

“…ErbB4, on the other hand, is associated with growth suppression and better prognosis. Interestingly, it exists in the nucleus as a cleaved intracellular fragment instead of a full-length protein and when in the nucleus it causes growth inhibition and even apoptosis ( Muraoka-Cook et al, 2008 ; Stephenson et al, 2012 ). It has been speculated that these opposing effects on tumor progression might arise from the differential mechanisms of membrane-to-nucleus trafficking in different family members ( Carpenter and Liao, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

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EphA1 receptor tyrosine kinase is localized to the nucleus in rhabdomyosarcoma from multiple species

et al. 2022

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While the typical role of receptor tyrosine kinases is to receive and transmit signals at the cell surface, in some cellular contexts (particularly transformed cells) they may also act as nuclear proteins. Aberrant nuclear localization of receptor tyrosine kinases associated with transformation often enhances the transformed phenotype (i.e. nuclear ErbBs promote tumor progression in breast cancer). Rhabdomyosarcoma (RMS), the most common soft tissue tumor in children, develops to resemble immature skeletal muscle and has been proposed to derive from muscle stem/progenitor cells (satellite cells). It is an aggressive cancer with a 5-year survival rate of 33% if it has metastasized. Eph receptor tyrosine kinases have been implicated in the development and progression of many other tumor types, but there are only two published studies of Ephs localizing to the nucleus of any cell type and to date no nuclear RTKs have been identified in RMS. In a screen for protein expression of Ephs in canine RMS primary tumors as well as mouse and human RMS cell lines, we noted strong expression of EphA1 in the nucleus of interphase cells in tumors from all three species. This localization pattern changes in dividing cells, with EphA1 localizing to the nucleus or the cytoplasm depending on the phase of the cell cycle. These data represent the first case of a nuclear RTK in RMS, and the first time that EphA1 has been detected in the nucleus of any cell type.

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Signaling of Receptor Tyrosine Kinases in the Nucleus

Cited by 5 publications

References 131 publications

EphB4 localises to the nucleus of prostate cancer cells

EphB4 localises to the nucleus of prostate cancer cells

Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases

EphA1 receptor tyrosine kinase is localized to the nucleus in rhabdomyosarcoma from multiple species

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