Possible role of protein kinase C in the regulation of intracellular stability of focal adhesion kinase in mouse 3T3 cells

Mogi, Akira; Hatai, Mika; Soga, Hisae; Takenoshita, Seiichi; Nagamachi, Yukio; Fujimoto, Jiro; Yamamoto, Tadashi; Yokota, Jun; Yaoi, Yoshihito

doi:10.1016/0014-5793(95)01014-6

Cited by 16 publications

(8 citation statements)

References 25 publications

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“…In contrast, only mAChR-mediated myosin reorganization is inhibited by Go6976, which specifically antagonizes conventional PKC isoforms (36). It is generally believed that PKC activation is required for cell spreading, and other signals are required for cytoskeletal reorganization (45)(46)(47)(48)(49)(50)(51). Our findings suggest that while the novel PKC isoforms are needed for cell spreading, the conventional PKC isoforms are needed for myosin reorganization.…”

Section: Discussionmentioning

confidence: 45%

M3 Muscarinic Acetylcholine Receptors Regulate Cytoplasmic Myosin by a Process Involving RhoA and Requiring Conventional Protein Kinase C Isoforms

Strassheim

May

Varker

et al. 1999

Journal of Biological Chemistry

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Contractile processes in non-muscle cells mimic those occurring in smooth muscle tissues, indicating the value of using non-muscle cells to investigate the biochemical pathways that regulate contraction (4 -8). Phosphorylation of myosin light chains (MLC) in non-muscle cells causes the formation of myosin-containing stress fibers, which are contractile bundles of actin filaments associated with myosin II (4 -8). Phosphorylation of MLC similarly increases actin-myosin interactions in smooth muscle cells, resulting in smooth muscle contraction (reviewed in Refs. 9 -12). In addition to smooth muscle contraction, many fundamental cellular processes such as adhesion, migration, and division depend upon the interaction of myosin with actin in contractile filaments (reviewed in Ref. 12). Activation of mAChR may affect these fundamental processes by altering myosin activity in non-muscle cells as it does in smooth muscle. Although mAChR activation induces MLC phosphorylation and subsequent contraction in smooth muscle cells (13)(14)(15)(16)(17), the ability of mAChR to regulate MLC phosphorylation and myosin organization in non-muscle cells has not been reported.We investigated the ability of transfected human mAChR subtypes to regulate myosin organization in Chinese hamster ovary (CHO) cells. Activation of transfected M 3 mAChR induces MLC phosphorylation and causes myosin-containing stress fibers to form in CHO cells. The involvement of PKC in these events is indicated by our findings that 1) direct activation of PKC with phorbol esters induces MLC phosphorylation and myosin reorganization in CHO cells, 2) specific PKC antagonists inhibit M 3 mAChR-mediated myosin reorganization, and 3) activation of transfected M 1 but not M 2 mAChR subtypes also induces the formation of myosin-containing stress fibers, demonstrating that only mAChR subtypes that stimulate PKC activity induce myosin reorganization. The participation of myosin light chain kinase (MLCK) and RhoA in mAChRmediated myosin reorganization was also investigated, since these proteins regulate contractile processes in other systems

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Section: Discussionmentioning

confidence: 45%

M3 Muscarinic Acetylcholine Receptors Regulate Cytoplasmic Myosin by a Process Involving RhoA and Requiring Conventional Protein Kinase C Isoforms

Strassheim

May

Varker

et al. 1999

Journal of Biological Chemistry

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“…(Fibroblasts and myeloid progenitors express the heterodimeric adhesion molecule integrin ␣5␤1, which is the receptor for the extracellular matrix protein fibronectin. 1,11,30 This ligand binding signal may still trigger normal signal transduction pathways, causing changes in the cytoskeleton and morphology, which may partially reverse the reduced actin polymerization caused by BCR-ABL expression. Interestingly, in SRC-transfected chicken embryo fibroblasts, there is a decrease in fibronectin deposition outside of the cells, accompanied by abrogation of cell adhesion.…”

Section: Discussionmentioning

confidence: 99%

Reduced focal adhesion kinase and paxillin phosphorylation in BCR‐ABL‐transfected cells

Cheng

Kurzrock

Qiu

et al. 2002

Cancer

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BACKGROUNDBCR‐ABL formation is critical to oncogenic transformation in chronic myelogenous leukemia and has been implicated as a key event leading to alterations in cytoskeletal structures and adhesion in the leukemic cells. The authors therefore investigated the effect of p210BCR‐ABL on actin polymerization as well as on the expression and phosphorylation state of the adhesion proteins paxillin and focal adhesion kinase (FAK).METHODSTransfection with BCR‐ABL constructs abrogated the ability of NIH 3T3 fibroblasts to adhere and the cells underwent striking morphologic changes.RESULTSScanning electron microscopy revealed that the cells lost their elongated appearance and became rounded. This alteration was associated with significantly reduced actin polymerization. In addition, steady‐state levels of paxillin and FAK protein were increased. However, while the overall level of phosphotyrosines was also increased, the amount of tyrosine phosphorylated paxillin and FAK was reduced in the BCR‐ABL‐transfected cells as compared to the parental cells. Culture on extracellular fibronectin matrix partially reversed the morphologic changes and resulted in a return, albeit incomplete, of filamentous actin in BCR‐ABL‐transfected 3T3 fibroblasts. In addition, phosphorylation of paxillin and FAK in the BCR‐ABL‐transfected NIH 3T3 cells was restored.CONCLUSIONSThe authors conclude that, in the current system, transfection of BCR‐ABL attenuates FAK and paxillin phosphorylation and reduces actin polymerization, events accompanied by significant alterations in cellular morphology. The observation that exposure of the cells to fibronectin partially reverses all these changes suggests that the focal adhesion proteins and actin structures nevertheless remain responsive to singnaling from the outside. Cancer 2002;95:440–50. © 2002 American Cancer Society.DOI 10.1002/cncr.10670

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“…vinculin (Werth et al, 1983), talin (Meenakshi et al, 1993), filamin (Tigges et al, 2003) and integrins (Rabinovitz et al, 2004)]. PKC isoforms have also been shown to induce activation of focal adhesion-localized ERK1/2 (Besson et al, 2001;Howe and Juliano, 1998;Rigot et al, 1998), RhoA (Dovas et al, 2006) and FAK (Mogi et al, 1995), events that lead to an increase in focal adhesion number, cell adhesion and/or cell migration. Similar to what we report here for PKC-mediated SH2B1b release from focal adhesions, our recent work suggests that activation of PKC with subsequent phosphorylation of SH2B1b at Ser161 and Ser165 also releases SH2B1b from the plasma membrane (Maures et al, 2011).…”

Section: Sh2b1b Is a New Focal Adhesion Protein 3101mentioning

confidence: 99%

Identification of SH2B1β as a focal adhesion protein that regulates focal adhesion size and number

Lanning

Argetsinger

et al. 2011

Journal of Cell Science

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SummaryThe adaptor protein SH2B1b participates in regulation of the actin cytoskeleton during processes such as cell migration and differentiation. Here, we identify SH2B1b as a new focal adhesion protein. We provide evidence that SH2B1b is phosphorylated in response to phorbol 12-myristate 13-acetate (PMA)-induced protein kinase C (PKC) activation and show that PMA induces a rapid redistribution of SH2B1b out of focal adhesions. We also show that growth hormone (GH) increases cycling of SH2B1b into and out of focal adhesions. Ser161 and Ser165 in SH2B1b fall within consensus PKC substrate motifs. Mutating these two serine residues into alanine residues abrogates PMA-induced redistribution of SH2B1b out of focal adhesions, decreases SH2B1b cycling into and out of focal adhesions in control and GH-stimulated cells, and increases the size of focal adhesions. By contrast, mutating Ser165 into a glutamate residue decreases the amount of SH2B1b in focal adhesions and increases the number of focal adhesions per cell. These results suggest that activation of PKC regulates SH2B1b focal adhesion localization through phosphorylation of Ser161 and/or Ser165. The finding that phosphorylation of SH2B1b increases the number of focal adhesions suggests a mechanism for the stimulatory effect on cell motility of SH2B1b.

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Possible role of protein kinase C in the regulation of intracellular stability of focal adhesion kinase in mouse 3T3 cells

Cited by 16 publications

References 25 publications

M3 Muscarinic Acetylcholine Receptors Regulate Cytoplasmic Myosin by a Process Involving RhoA and Requiring Conventional Protein Kinase C Isoforms

M3 Muscarinic Acetylcholine Receptors Regulate Cytoplasmic Myosin by a Process Involving RhoA and Requiring Conventional Protein Kinase C Isoforms

Reduced focal adhesion kinase and paxillin phosphorylation in BCR‐ABL‐transfected cells

Identification of SH2B1β as a focal adhesion protein that regulates focal adhesion size and number

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