Src kinase modulates the activation, transport and signalling dynamics of fibroblast growth factor receptors

Research output: Contribution to journalArticle

Standard

Src kinase modulates the activation, transport and signalling dynamics of fibroblast growth factor receptors. / Sandilands, E; Akbarzadeh, S; Vecchione, A; McEwan, DG; Frame, MC; Heath, John.

In: EMBO Reports, Vol. 8, No. 12, 01.12.2007, p. 1162-1169.

Research output: Contribution to journalArticle

Harvard

APA

Vancouver

Author

Sandilands, E ; Akbarzadeh, S ; Vecchione, A ; McEwan, DG ; Frame, MC ; Heath, John. / Src kinase modulates the activation, transport and signalling dynamics of fibroblast growth factor receptors. In: EMBO Reports. 2007 ; Vol. 8, No. 12. pp. 1162-1169.

Bibtex

@article{4fabd81f9eb0450fbbf8579c21d3ace4,
title = "Src kinase modulates the activation, transport and signalling dynamics of fibroblast growth factor receptors",
abstract = "The non-receptor tyrosine kinase Src is recruited to activated fibroblast growth factor receptor (FGFR) complexes through the adaptor protein factor receptor substrate 2 (FRS2). Here, we show that Src kinase activity has a crucial role in the regulation of FGFR1 signalling dynamics. Following receptor activation by ligand binding, activated Src is colocalized with activated FGFR1 at the plasma membrane. This localization requires both active Src and FGFR1 kinases, which are inter-dependent. Internalization of activated FGFR1 is associated with release from complexes containing activated Src. Src-mediated transport and subsequent activation of FGFR1 require both RhoB endosomes and an intact actin cytoskeleton. Chemical and genetic inhibition studies showed strikingly different requirements for Src family kinases in FGFR1-mediated signalling; activation of the phosphoinositide-3 kinase-Akt pathway is severely attenuated, whereas activation of the extracellular signal-regulated kinase pathway is delayed in its initial phase and fails to attenuate.",
keywords = "actin, Src, RhoB, FGFR, phosphorylation",
author = "E Sandilands and S Akbarzadeh and A Vecchione and DG McEwan and MC Frame and John Heath",
year = "2007",
month = dec
day = "1",
doi = "10.1038/sj.embor.7401097",
language = "English",
volume = "8",
pages = "1162--1169",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "EMBO Press",
number = "12",

}

RIS

TY - JOUR

T1 - Src kinase modulates the activation, transport and signalling dynamics of fibroblast growth factor receptors

AU - Sandilands, E

AU - Akbarzadeh, S

AU - Vecchione, A

AU - McEwan, DG

AU - Frame, MC

AU - Heath, John

PY - 2007/12/1

Y1 - 2007/12/1

N2 - The non-receptor tyrosine kinase Src is recruited to activated fibroblast growth factor receptor (FGFR) complexes through the adaptor protein factor receptor substrate 2 (FRS2). Here, we show that Src kinase activity has a crucial role in the regulation of FGFR1 signalling dynamics. Following receptor activation by ligand binding, activated Src is colocalized with activated FGFR1 at the plasma membrane. This localization requires both active Src and FGFR1 kinases, which are inter-dependent. Internalization of activated FGFR1 is associated with release from complexes containing activated Src. Src-mediated transport and subsequent activation of FGFR1 require both RhoB endosomes and an intact actin cytoskeleton. Chemical and genetic inhibition studies showed strikingly different requirements for Src family kinases in FGFR1-mediated signalling; activation of the phosphoinositide-3 kinase-Akt pathway is severely attenuated, whereas activation of the extracellular signal-regulated kinase pathway is delayed in its initial phase and fails to attenuate.

AB - The non-receptor tyrosine kinase Src is recruited to activated fibroblast growth factor receptor (FGFR) complexes through the adaptor protein factor receptor substrate 2 (FRS2). Here, we show that Src kinase activity has a crucial role in the regulation of FGFR1 signalling dynamics. Following receptor activation by ligand binding, activated Src is colocalized with activated FGFR1 at the plasma membrane. This localization requires both active Src and FGFR1 kinases, which are inter-dependent. Internalization of activated FGFR1 is associated with release from complexes containing activated Src. Src-mediated transport and subsequent activation of FGFR1 require both RhoB endosomes and an intact actin cytoskeleton. Chemical and genetic inhibition studies showed strikingly different requirements for Src family kinases in FGFR1-mediated signalling; activation of the phosphoinositide-3 kinase-Akt pathway is severely attenuated, whereas activation of the extracellular signal-regulated kinase pathway is delayed in its initial phase and fails to attenuate.

KW - actin

KW - Src

KW - RhoB

KW - FGFR

KW - phosphorylation

U2 - 10.1038/sj.embor.7401097

DO - 10.1038/sj.embor.7401097

M3 - Article

C2 - 17975556

VL - 8

SP - 1162

EP - 1169

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

IS - 12

ER -