Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion-associated tyrosine kinase.

Kornberg, Lori; Earp, H. Shelton; Parsons, J. Thomas; Schaller, Michael D.; Juliano, R. L.

doi:10.1016/s0021-9258(18)35853-8

Cited by 664 publications

(97 citation statements)

References 30 publications

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“…A complete understanding of the role of autophosphorylation in regulating the association of proteins with pp125FAK awaits future analysis. pp125FAK becomes tyrosine phosphorylated when fibroblasts adhere to ECM proteins and upon the activation of resting platelets (4,14,16,24,29,49). Concomitantly, ppl25FA becomes enzymatically activated, as measured in an in vitro kinase assay (14,29).…”

Section: Discussionmentioning

confidence: 99%

“…The PTK pp125FAK is phosphorylated on tyrosine in response to the engagement of cell surface integrins with com-ponents of the ECM (4, 14,16,24,29,49), and concomitantly, its enzymatic activity, measured in vitro, is elevated (14,29). Furthermore, pp125FAK forms a stable complex with pp6o0rc in src-transformed chicken embryo (CE) cells and is found in complex with pp59C-Yfy in normal CE cells (7).…”

mentioning

confidence: 99%

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Autophosphorylation of the Focal Adhesion Kinase, ppl25^FAK, Directs SH2-Dependent Binding of pp60^src

Schaller

Hildebrand

Shannon

et al. 1994

Molecular and Cellular Biology

393

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The phosphorylation of protein tyrosine kinases (PTKs) on tyrosine residues is a critical regulatory event that modulates catalytic activity and triggers the physical association of PTKs with Src homology 2 (SH2)-containing proteins. The integrin-linked focal adhesion kinase, pp125FAK, exhibits extracellular matrix-dependent phosphorylation on tyrosine and physically associates with two nonreceptor PTKs, pp60src and pp59fyn, via their SH2 domains. Herein, we identify Tyr-397 as the major site of tyrosine phosphorylation on pp125FAK both in vivo and in vitro. Tyrosine 397 is located at the juncture of the N-terminal and catalytic domains, a novel site for PTK autophosphorylation. Mutation of Tyr-397 to a nonphosphorylatable residue dramatically impairs the phosphorylation of pp125FAK on tyrosine in vivo and in vitro. The mutation of Tyr-397 to Phe also inhibits the formation of stable complexes with pp60src in cells expressing Src and FAK397F, suggesting that autophosphorylation of pp125FAK may regulate the association of pp125FAK with Src family kinases in vivo. The identification of Tyr-397 as a major site for FAK autophosphorylation provides one of the first examples of a cellular protein containing a high-affinity binding site for a Src family kinase SH2 domain. This finding has implications for models describing the mechanisms of action of pp125FAK, the regulation of the Src family of PTKs, and signal transduction through the integrins.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Autophosphorylation of the Focal Adhesion Kinase, ppl25^FAK, Directs SH2-Dependent Binding of pp60^src

Schaller

Hildebrand

Shannon

et al. 1994

Molecular and Cellular Biology

393

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“…Bar, 20 µm. Hanks et al, 1992;Kornberg et al, 1992;Romer et al, 1992Romer et al, , 1994, we examined FAK phosphorylation in serum-stimu-lated, quiescent Swiss 3T3 fibroblasts. Immunoprecipitated FAK was heavily phosphorylated on tyrosine in confluent Swiss 3T3 fibroblasts grown in 10% BCS (Fig.…”

Section: Serum-induced Reorganization Of the Cytoskeleton Is Accompanied By Changes In Fak Phosphorylationmentioning

confidence: 99%

“…One of the major tyrosine phosphorylated, focal adhesion proteins is itself a tyrosine kinase, the focal adhesion kinase (FAK) (Hanks et al, 1992;Schaller et al, 1992;Whitney et al, 1993). FAK becomes tyrosine phosphorylated and activated in response to either integrin-mediated adhesion (Guan and Shalloway, 1992;Burridge et al, 1992b;Hanks et al, 1992;Kornberg et al, 1992;Lipfert et al, 1992;Romer et al, 1992Romer et al, , 1994, or integrin clustering by antibodies (Kornberg et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Tyrosine phosphorylation is involved in reorganization of the actin cytoskeleton in response to serum or LPA stimulation

Chrzanowska‐Wodnicka

Burridge

1994

Journal of Cell Science

133

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Tyrosine phosphorylation is known to regulate the formation of focal adhesions in cells adhering to extracellular matrix (ECM). We have investigated the possible involvement of tyrosine phosphorylation and the focal adhesion kinase (FAK) in the cytoskeletal changes induced by serum or lysophosphatidic acid (LPA) in quiescent Swiss 3T3 fibroblasts. As shown previously by others, quiescent cells stimulated with serum or LPA reveal a rapid reappearance of focal adhesions and stress fibers. Here we show that this is accompanied by an increase in phosphotyrosine in focal adhesions and specifically an increase in the tyrosine phosphorylation of FAK. The LPA-stimulated reappearance of focal adhesions and stress fibers is blocked by inhibitors of phospholipase C but not by pertussis toxin (PTX), indicating that this LPA signaling pathway is mediated by phospholipase C activation and does not involve PTX-sensitive G proteins. In the absence of serum or LPA, these cytoskeletal effects and the tyrosine phosphorylation of FAK can be mimicked by sodium orthovanadate in conjunction with hydrogen peroxide, agents that inhibit protein tyrosine phosphatases and thereby elevate levels of phosphotyrosine. Two tyrosine kinase inhibitors, erbstatin and genistein block both the serum-induced tyrosine phosphorylation of FAK and the assembly of focal adhesions and stress fibers. Two other tyrosine kinase inhibitors, tyrphostins 47 and 25, previously shown to inhibit FAK, failed to prevent FAK phosphorylation or the reassembly of focal adhesions and stress fibers in response to serum. However, these inhibitors did prevent FAK phosphorylation and cytoskeletal assembly in response to lysophosphatidic acid (LPA), one component of serum previously shown to stimulate assembly of focal adhesions and stress fibers. Our findings suggest that the response to serum is complex and that although FAK phosphorylation is important, other tyrosine kinases may also be involved.

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“…Ερεθίσµατα που ενεργοποιούν την FAΚ κινάση είναι νευροπεπτίδια (Seufferlein and Rozengurt 1995;Sinnett-Smith et al 1993;Zachary et al 1992;Zachary et al 1993), αυξητικοί παράγοντες όπως ο PDGF (Rankin and Rozengurt 1994;Saito et al 1996), ο EGF (Pichard et al 2001;Tapia et al 1999) ο ΗGF (Baron et al 1998;Beviglia and Kramer 1999;Chen et al 1998;Liu et al 2002), ο ILGF-1 (Casamassima and Rozengurt 1998;Gleeson et al 2001) ο VEGF (Qi and Claesson-Welsh 2001;Rousseau et al 2000;Takahashi et al 1999), ορµόνες (Koukouritaki et al 1999a;Papakonstanti et al 2003), η θροµβίνη (Schaphorst et al 1997), ο παράγοντας νέκρωσης καρκινικών κυττάρων (Koukouritaki et al 1999b), βιοδραστικά λιπίδια όπως ο LPA (Hordijk et al 1994;Kumagai et al 1993;Seufferlein and Rozengurt 1994) φωρφβολεστέρες και εξωκυττάριες πρωτεΐνες (Burridge et al 1992;Guan and Shalloway 1992;Kornberg et al 1992;Lipfert et al 1992;Vuori and Ruoslahti 1993).…”

Section: εστίες πρόσφυσης των κυττάρων ο ρόλος της Fak και της βινκουλίνης στα κύτταραunclassified

Μελέτη Των Μεταβολών Της Δυναμική Ισορροπίας Της Ακτίνης Στην Βιολογία Του Καρκίνου

Kallergi¹,

Καλλέργη²

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Εκπόνηση διδακτορικής διατριβής µε θέµα « Μελέτη των µεταβολών της δυναµικής ισορροπίας της ακτίνης στην βιολογία του καρκίνου». Μέθοδοι: Western blot ανάλυση της πολυµερισµένης και µη ακτίνης σε καρκινικές και φυσιολογικές σειρές κυττάρων. Ανάλυση DNA-ασης των επιπέδων της ακτινής στα κύτταρα αυτά. Ανοσοεντοπισµός της ακτίνης σε όλες τις κυτταρικές σειρές. Χρήση οπτικού και confocal laser µικροσκοπίου για µορφολογική µελέτη του κυτταροσκελετού.

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Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion-associated tyrosine kinase.

Cited by 664 publications

References 30 publications

Autophosphorylation of the Focal Adhesion Kinase, ppl25^FAK, Directs SH2-Dependent Binding of pp60^src

Autophosphorylation of the Focal Adhesion Kinase, ppl25^FAK, Directs SH2-Dependent Binding of pp60^src

Tyrosine phosphorylation is involved in reorganization of the actin cytoskeleton in response to serum or LPA stimulation

Μελέτη Των Μεταβολών Της Δυναμική Ισορροπίας Της Ακτίνης Στην Βιολογία Του Καρκίνου

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Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion-associated tyrosine kinase.

Cited by 664 publications

References 30 publications

Autophosphorylation of the Focal Adhesion Kinase, ppl25FAK, Directs SH2-Dependent Binding of pp60src

Autophosphorylation of the Focal Adhesion Kinase, ppl25FAK, Directs SH2-Dependent Binding of pp60src

Tyrosine phosphorylation is involved in reorganization of the actin cytoskeleton in response to serum or LPA stimulation

Μελέτη Των Μεταβολών Της Δυναμική Ισορροπίας Της Ακτίνης Στην Βιολογία Του Καρκίνου

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Autophosphorylation of the Focal Adhesion Kinase, ppl25^FAK, Directs SH2-Dependent Binding of pp60^src

Autophosphorylation of the Focal Adhesion Kinase, ppl25^FAK, Directs SH2-Dependent Binding of pp60^src