Receptor tyrosine kinase-G-protein coupled receptor complex signaling in mammalian cells

N.J. Pyne, C. Waters, J.S.L. Long, N. Akhtar Moughal, G. Tigyi, S. Pyne

Research output: Contribution to journalLiterature review

21 Citations (Scopus)

Abstract

Recent evidence suggests that signals transmitted by receptor tyrosine kinases (RTK) and G-protein coupled receptors (GPCR) are integrated to promote efficient growth factor stimulation of cellular responses (Waters et al., 2004). The important feature of this model is that agents that disrupt GPCR function (e.g. pertussis toxin (PTX) and the C-terminal tail of GRK2, which sequesters Gbg subunits) block the growth factor-stimulated activation of various effector modules, such as p42/p44 mitogen activated protein kinase (p42/p44 MAPK) (Luttrell et al., 1995; Fedorov et al., 1998; Conway et al., 1999; Alderton et al., 2001; Waters et al., 2003). This invokes a role for GPCR and places the G-protein down-stream from the RTK. There is now a body of evidence which supports this type of model in mammalian cells. For instance, the IGF-1 and FGF receptors use the G-protein, Gi to stimulate activation of p42/p44 MAPK in fibroblasts and skeletal muscle, respectively (Luttrell et al., 1995; Fedorov et al., 1998). We have also reported that the platelet derived growth factor (PDGF)-induced activation of c-Src and p42/p44 MAPK can be reduced by PTX and CT-GRK2 in airway smooth muscle (ASM) cells and HEK 293 cells (Conway et al., 1999; Alderton et al., 2001; Waters et al., 2003) and that the overexpression
of Gia2 enhances the stimulation of p42/p44 MAPK by PDGF, associated with
a PDGFb receptor kinase-catalyzed tyrosine phosphorylation of Gia2 (Alderton et al., 2001). The tyrosine phosphorylation of endogenous Gia2 might prevent reformation of the inactive Gabg complex, thereby prolonging the lifetime of active G-protein subunits, including Gbg. The integrative signal mechanism is distinct from the transactivation of RTK by GPCR agonists, which involves stimulation of the tyrosine phosphorylation of the RTK.
LanguageEnglish
Pages271-280
Number of pages10
JournalAdvances in Enzyme Regulation
Volume47
Issue number1
DOIs
Publication statusPublished - 2007

Fingerprint

Mitogen-Activated Protein Kinase 1
Receptor Protein-Tyrosine Kinases
G-Protein-Coupled Receptors
GTP-Binding Proteins
Platelet-Derived Growth Factor
Pertussis Toxin
Phosphorylation
Intercellular Signaling Peptides and Proteins
Fibroblast Growth Factor Receptors
IGF Type 1 Receptor
HEK293 Cells
Protein Subunits
Protein-Tyrosine Kinases
Transcriptional Activation
Smooth Muscle Myocytes
Tyrosine
Skeletal Muscle
Fibroblasts

Keywords

  • receptor tyrosine kinases
  • G-protein coupled receptors

Cite this

Pyne, N.J. ; Waters, C. ; Long, J.S.L. ; Akhtar Moughal, N. ; Tigyi, G. ; Pyne, S. / Receptor tyrosine kinase-G-protein coupled receptor complex signaling in mammalian cells. In: Advances in Enzyme Regulation. 2007 ; Vol. 47, No. 1. pp. 271-280.
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abstract = "Recent evidence suggests that signals transmitted by receptor tyrosine kinases (RTK) and G-protein coupled receptors (GPCR) are integrated to promote efficient growth factor stimulation of cellular responses (Waters et al., 2004). The important feature of this model is that agents that disrupt GPCR function (e.g. pertussis toxin (PTX) and the C-terminal tail of GRK2, which sequesters Gbg subunits) block the growth factor-stimulated activation of various effector modules, such as p42/p44 mitogen activated protein kinase (p42/p44 MAPK) (Luttrell et al., 1995; Fedorov et al., 1998; Conway et al., 1999; Alderton et al., 2001; Waters et al., 2003). This invokes a role for GPCR and places the G-protein down-stream from the RTK. There is now a body of evidence which supports this type of model in mammalian cells. For instance, the IGF-1 and FGF receptors use the G-protein, Gi to stimulate activation of p42/p44 MAPK in fibroblasts and skeletal muscle, respectively (Luttrell et al., 1995; Fedorov et al., 1998). We have also reported that the platelet derived growth factor (PDGF)-induced activation of c-Src and p42/p44 MAPK can be reduced by PTX and CT-GRK2 in airway smooth muscle (ASM) cells and HEK 293 cells (Conway et al., 1999; Alderton et al., 2001; Waters et al., 2003) and that the overexpressionof Gia2 enhances the stimulation of p42/p44 MAPK by PDGF, associated witha PDGFb receptor kinase-catalyzed tyrosine phosphorylation of Gia2 (Alderton et al., 2001). The tyrosine phosphorylation of endogenous Gia2 might prevent reformation of the inactive Gabg complex, thereby prolonging the lifetime of active G-protein subunits, including Gbg. The integrative signal mechanism is distinct from the transactivation of RTK by GPCR agonists, which involves stimulation of the tyrosine phosphorylation of the RTK.",
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year = "2007",
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Receptor tyrosine kinase-G-protein coupled receptor complex signaling in mammalian cells. / Pyne, N.J.; Waters, C.; Long, J.S.L.; Akhtar Moughal, N.; Tigyi, G.; Pyne, S.

In: Advances in Enzyme Regulation, Vol. 47, No. 1, 2007, p. 271-280.

Research output: Contribution to journalLiterature review

TY - JOUR

T1 - Receptor tyrosine kinase-G-protein coupled receptor complex signaling in mammalian cells

AU - Pyne, N.J.

AU - Waters, C.

AU - Long, J.S.L.

AU - Akhtar Moughal, N.

AU - Tigyi, G.

AU - Pyne, S.

PY - 2007

Y1 - 2007

N2 - Recent evidence suggests that signals transmitted by receptor tyrosine kinases (RTK) and G-protein coupled receptors (GPCR) are integrated to promote efficient growth factor stimulation of cellular responses (Waters et al., 2004). The important feature of this model is that agents that disrupt GPCR function (e.g. pertussis toxin (PTX) and the C-terminal tail of GRK2, which sequesters Gbg subunits) block the growth factor-stimulated activation of various effector modules, such as p42/p44 mitogen activated protein kinase (p42/p44 MAPK) (Luttrell et al., 1995; Fedorov et al., 1998; Conway et al., 1999; Alderton et al., 2001; Waters et al., 2003). This invokes a role for GPCR and places the G-protein down-stream from the RTK. There is now a body of evidence which supports this type of model in mammalian cells. For instance, the IGF-1 and FGF receptors use the G-protein, Gi to stimulate activation of p42/p44 MAPK in fibroblasts and skeletal muscle, respectively (Luttrell et al., 1995; Fedorov et al., 1998). We have also reported that the platelet derived growth factor (PDGF)-induced activation of c-Src and p42/p44 MAPK can be reduced by PTX and CT-GRK2 in airway smooth muscle (ASM) cells and HEK 293 cells (Conway et al., 1999; Alderton et al., 2001; Waters et al., 2003) and that the overexpressionof Gia2 enhances the stimulation of p42/p44 MAPK by PDGF, associated witha PDGFb receptor kinase-catalyzed tyrosine phosphorylation of Gia2 (Alderton et al., 2001). The tyrosine phosphorylation of endogenous Gia2 might prevent reformation of the inactive Gabg complex, thereby prolonging the lifetime of active G-protein subunits, including Gbg. The integrative signal mechanism is distinct from the transactivation of RTK by GPCR agonists, which involves stimulation of the tyrosine phosphorylation of the RTK.

AB - Recent evidence suggests that signals transmitted by receptor tyrosine kinases (RTK) and G-protein coupled receptors (GPCR) are integrated to promote efficient growth factor stimulation of cellular responses (Waters et al., 2004). The important feature of this model is that agents that disrupt GPCR function (e.g. pertussis toxin (PTX) and the C-terminal tail of GRK2, which sequesters Gbg subunits) block the growth factor-stimulated activation of various effector modules, such as p42/p44 mitogen activated protein kinase (p42/p44 MAPK) (Luttrell et al., 1995; Fedorov et al., 1998; Conway et al., 1999; Alderton et al., 2001; Waters et al., 2003). This invokes a role for GPCR and places the G-protein down-stream from the RTK. There is now a body of evidence which supports this type of model in mammalian cells. For instance, the IGF-1 and FGF receptors use the G-protein, Gi to stimulate activation of p42/p44 MAPK in fibroblasts and skeletal muscle, respectively (Luttrell et al., 1995; Fedorov et al., 1998). We have also reported that the platelet derived growth factor (PDGF)-induced activation of c-Src and p42/p44 MAPK can be reduced by PTX and CT-GRK2 in airway smooth muscle (ASM) cells and HEK 293 cells (Conway et al., 1999; Alderton et al., 2001; Waters et al., 2003) and that the overexpressionof Gia2 enhances the stimulation of p42/p44 MAPK by PDGF, associated witha PDGFb receptor kinase-catalyzed tyrosine phosphorylation of Gia2 (Alderton et al., 2001). The tyrosine phosphorylation of endogenous Gia2 might prevent reformation of the inactive Gabg complex, thereby prolonging the lifetime of active G-protein subunits, including Gbg. The integrative signal mechanism is distinct from the transactivation of RTK by GPCR agonists, which involves stimulation of the tyrosine phosphorylation of the RTK.

KW - receptor tyrosine kinases

KW - G-protein coupled receptors

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U2 - 10.1016/j.advenzreg.2006.12.011

DO - 10.1016/j.advenzreg.2006.12.011

M3 - Literature review

VL - 47

SP - 271

EP - 280

JO - Advances in Enzyme Regulation

T2 - Advances in Enzyme Regulation

JF - Advances in Enzyme Regulation

SN - 0065-2571

IS - 1

ER -