G Protein-coupled Receptor Activation Rapidly Stimulates Focal Adhesion Kinase Phosphorylation at Ser-843

Fan, Robert S.; Jácamo, Rodrigo; Jiang, Xiaohua; Sinnett‐Smith, James; Rozengurt, Enrique

doi:10.1074/jbc.m500716200

Cited by 56 publications

(60 citation statements)

References 60 publications

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“…Recent results from our laboratory demonstrated that FAK phosphorylation at Ser-910 was strikingly stimulated by GPCR agonists, tumor promoting phorbol esters and growth factors in Swiss 3T3 fibroblasts [34][35][36]. Furthermore, phosphorylation of FAK at Ser-843 was induced by GPCR agonists, including bombesin, vasopressin and bradykinin in Swiss 3T3 fibroblasts [37]. These results indicate that phosphorylation of FAK at serine residues can be regulated by external stimuli including GPCRs and growth factors.…”

Section: Discussionmentioning

confidence: 63%

“…Recent results from our laboratory demonstrated that FAK phosphorylation at Ser-910 is strikingly stimulated by GPCR agonists, tumor promoting phorbol esters and growth factors through an ERK-dependent pathway in Swiss 3T3 fibroblasts [34][35][36]. In another study, we demonstrated that stimulation of 3T3 fibroblasts with bombesin, bradykinin or vasopressin induced a rapid and transient increase in FAK phosphorylation at Ser-843 through a Ca 2+ /calmodulin/CaMKII-dependent pathway [37]. These findings support the hypothesis that FAK phosphorylation at both, tyrosine and serine residues is modulated by a variety of stimuli but do not exclude the possibility that FAK phosphorylation at tyrosine and serine residues could be regulated differentially in some cell types.…”

Section: Introductionmentioning

confidence: 69%

“…In fibroblasts, we proposed that FAK serves as a point of integration of signals transmitted via Gα q , leading to PKC/ERK-dependent FAK phosphorylation at Ser-910 [34][35][36] and to Ca 2+ /calmodulin/CaMKII-dependent FAK phosphorylation at Ser-843 [37]. Here, we examined whether these pathways also operate in intestinal epithelial cells.…”

Section: Discussionmentioning

confidence: 98%

“…Recently, we demonstrated FAK phosphorylation at Ser-843 through a Ca 2+ , calmodulin and CaMKII-dependent pathway in mouse fibroblasts [37]. As a first step to examine whether an increase in [Ca 2+ ] i could trigger FAK phosphorylation at Ser-843 in epithelial cells, cultures of IEC-18 cells were treated with the Ca 2+ ionophore ionomycin for various times, at a concentration (500 nM) that rapidly increases [Ca 2+ ] i in these cells (results not shown).…”

Section: Ionomycin and Gpcr Agonists Induce A Rapid And Transient Incmentioning

confidence: 99%

“…More recently, it has become clear that FAK is also phosphorylated at multiple serine residues [32][33][34][35][36][37]. The proximity of these phosphorylated serine residues to sites at which FAK interacts with other proteins suggests a possible function in the regulation of the assembly of FAK signaling complexes [6].…”

Section: Introductionmentioning

confidence: 99%

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Differential FAK phosphorylation at Ser-910, Ser-843 and Tyr-397 induced by angiotensin II, LPA and EGF in intestinal epithelial cells

Jiang

Sinnett‐Smith

2007

Cellular Signalling

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A rapid increase in the tyrosine phosphorylation of the non-receptor tyrosine kinase FAK is a prominent early event in fibroblasts stimulated by a variety of signaling molecules. However, a variety of epithelial cells, including intestinal epithelial cells, show a high basal level of tyrosine phosphorylated FAK that is only slightly further increased by addition of G protein-coupled receptors (GPCR) agonists or growth factors. In this study, we determined whether these stimuli could elicit FAK phosphorylation at serine residues, including Ser-910 and Ser-843. Our results show that multiple agonists including angiotensin II (ANGII), lysophosphatidic acid (LPA), phorbol esters and EGF induced a striking stimulation of FAK phosphorylation at Ser-910 in rat intestinal epithelial IEC-18 cells via an ERK-dependent pathway. In striking contrast, none of these stimuli promoted a significant further increase in FAK phosphorylation at Tyr-397 in these cells. These results were extended using cultures of polarized human colonic epithelial T84 cells. We found that either carbachol or EGF promoted a striking ERK-dependent phosphorylation of FAK at Ser-910, but these agonists caused only slight stimulation of FAK at Tyr-397 in T84 cells. In addition, we demonstrated that GPCR agonists also induced a dramatic increase of FAK phosphorylation at Ser-843 in either IEC-18 or T84 cells. Our results indicate that Ser-910 and Ser-843, rather than Tyr-397, are prominent sites differentially phosphorylated in response to neurotransmitters, bioactive lipids, tumor promoters and growth factors in intestinal epithelial cells.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 98%

Section: Ionomycin and Gpcr Agonists Induce A Rapid And Transient Incmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Differential FAK phosphorylation at Ser-910, Ser-843 and Tyr-397 induced by angiotensin II, LPA and EGF in intestinal epithelial cells

Jiang

Sinnett‐Smith

2007

Cellular Signalling

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Analysis of the gastrin‐releasing peptide receptor gene in Italian patients with autism spectrum disorders

Seidita

Mirisola

D'Anna

et al. 2008

American J of Med Genetics Pt B

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The gastrin-releasing peptide receptor (GRPR) was implicated for the first time in the pathogenesis of Autism spectrum disorders (ASD) by Ishikawa-Brush et al. [Ishikawa-Brush et al. (1997): Hum Mol Genet 6: 1241-1250]. Since this original observation, only one association study [Marui et al. (2004): Brain Dev 26: 5-7] has further investigated, though unsuccessfully, the involvement of the GRPR gene in ASD. With the aim of contributing further information to this topic we have sequenced the entire coding region and the intron/exon junctions of the GRPR gene in 149 Italian autistic patients. The results of this study led to the identification of four novel point mutations, two of which, that is, C6S and L181F, involve amino acid changes identified in two patients with ASD and Rett syndrome, respectively. Both the leucine at position 181 and the cysteine at position 6 are strongly conserved in vertebrates. C6S and L181F mutant proteins were expressed in COS-7 and BALB/3T3 cells, but they did not affect either GRP's binding affinity or its potency for stimulating phospholipase C-mediated production of inositol 1,4,5-trisphosphate. In summary, our results do not provide support for a major role of the GRPR gene in ASD in the population of patients we have studied. However, there is a potential role of C6S and L181F mutations on GRPR function, and possibly in the pathogenesis of the autistic disorders in the two patients.

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CaMK‐II promotes focal adhesion turnover and cell motility by inducing tyrosine dephosphorylation of FAK and paxillin

Easley

Brown

Horwitz

et al. 2008

Cell Motil. Cytoskeleton

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Transient elevations in Ca 2+ have previously been shown to promote focal adhesion disassembly and cell motility through an unknown mechanism. In this study, evidence is provided to show that CaMK-II, a Ca 2+ /calmodulin dependent protein kinase, influences fibroblast adhesion and motility. TIRF microscopy reveals a dynamic population of CaMK-II at the cell surface in migrating cells. Inhibition of CaMK-II with two mechanistically distinct, membrane permeant inhibitors (KN-93 and myr-AIP) freezes lamellipodial dynamics, accelerates spreading on fibronectin, enlarges paxillin-containing focal adhesions and blocks cell motility. In contrast, constitutively active CaMK-II is not found at the cell surface, reduces cell attachment, eliminates paxillin from focal adhesions and decreases the phospho-tyrosine levels of both FAK and paxillin; all of these events can be reversed with myr-AIP. Thus, both CaMK-II inhibition and constitutive activation block cell motility through overstabilization or destabilization of focal adhesions, respectively. Coupled with the existence of transient Ca 2+ elevations and a dynamic CaMK-II population, these findings provide the first direct evidence that CaMK-II enables cell motility by transiently and locally stimulating tyrosine dephosphorylation of focal adhesion proteins to promote focal adhesion turnover. Cell Motil.

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G Protein-coupled Receptor Activation Rapidly Stimulates Focal Adhesion Kinase Phosphorylation at Ser-843

Cited by 56 publications

References 60 publications

Differential FAK phosphorylation at Ser-910, Ser-843 and Tyr-397 induced by angiotensin II, LPA and EGF in intestinal epithelial cells

Differential FAK phosphorylation at Ser-910, Ser-843 and Tyr-397 induced by angiotensin II, LPA and EGF in intestinal epithelial cells

Analysis of the gastrin‐releasing peptide receptor gene in Italian patients with autism spectrum disorders

CaMK‐II promotes focal adhesion turnover and cell motility by inducing tyrosine dephosphorylation of FAK and paxillin

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