Protein tyrosine kinase PYK2 involved in Ca2+-induced regulation of ion channel and MAP kinase functions

Lev, Sima; Moreno, Herman; Martínez, Ricardo; Canoll, Peter; Peles, Elior; Musacchio, José M.; Plowman, Gregory D.; Rudy, Bernardo; Schlessinger, Joseph

doi:10.1038/376737a0

Cited by 1,319 publications

(1,511 citation statements)

References 45 publications

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“…Additionally, LNCaP cells express an inactive form of FAK (Tremblay et al, 1996). PYK2-mediated functions are carried out by activating multiple downstream signaling molecules, including ERK/ MAPK (Lev et al, 1995), p38/MAPK (Pandey et al, 1999), c-Src (Dikic et al, 1996) and paxillin (Li and Earp, 1997), which lead to the differential regulation of cell adhesion in different cell types. While elevated ERK/MAPK, p38/MAPK and c-Src activities are correlated with increased PYK2 activity and enhanced adhesion in C-81 as well as PYK2 cDNA-transfected C-33 cells (Supplementary Figure 1A and 2), only ERK/ MAPK activity was consistently reduced by expressing the Y402F or the K457A-PYK2 mutants in C-81 cells, correlated with a decreased adhesion (Figure 6, Supplementary Figure 1B).…”

Section: Discussionmentioning

confidence: 99%

ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells

et al. 2007

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Aberrant regulation in the adhesive ability of cancer cells is closely associated with their metastatic activity. In this study, we examine the role of ErbB-2 in regulating the adhesive ability of androgen receptor (AR)-positive human prostate cancer (PCa) cells, the major cell population of PCa. Utilizing different LNCaP and MDA PCa2b cells as model systems, we found that ErbB-2 activity was correlated with PYK2 activity and adhesive ability in those cells. Increased ErbB-2 expression or activity in LNCaP C-33 cells enhanced PYK2 activation and cell adhesion, while the high PYK2 activity and the rapid adhesion of LNCaP C-81 cells were decreased by diminishing ErbB-2 expression or activity. Knockdown studies revealed the predominant role of ErbB-2 in regulating LNCaP C-81 cell adhesion. Coimmunoprecipitation showed that C-81 cells had increased interaction between ErbB-2 and PYK2. Elevated ErbB-2 activity in LNCaP cells correlated with increased ERK/MAPK activity and enhanced adhesive ability, which were abolished by the expression of K457A-PYK2 mutant or the treatment of PD98059, a MEK inhibitor. In summary, our data suggested that ErbB-2, via PYK2-ERK/MAPK, upregulates the adhesive ability of AR-positive human PCa cells.

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Section: Discussionmentioning

confidence: 99%

ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells

et al. 2007

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“…In these cellular settings Pyk2, a focal adhesion kinase related tyrosine kinase independently activated by Ca 2+ and phorbol esters (Lev et al, 1995), has recently been placed upstream of receptor tyrosine kinases in the signaling pathway from G q/11 -coupled receptors to ERKs (Eguchi et al, 1999;Solto , 1998). To better understand mitogenic signaling by G q/11 -coupled receptors in SCLC cells, a detailed analysis of the role of receptor tyrosine kinases like c-kit and of non-receptor tyrosine kinases such as Pyk2 should be enlightening in the future.…”

Section: Discussionmentioning

confidence: 99%

The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to Gq, Gi and G12 proteins

et al. 2000

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Neuropeptides like galanin produced and released by small cell lung cancer (SCLC) cells are considered principal mitogens in these tumors. We identi®ed the galanin receptor type 2 (GALR2) as the only galanin receptor expressed in H69 and H510 cells. Photoa nity labeling of G proteins in H69 cell membranes revealed that GALR2 activates G proteins of three subfamilies: G q , G i , and G 12 . In H69 cells, galanin-induced Ca 2+ mobilization was pertussis toxin-insensitive. While phorbol ester-induced extracellular signal-regulated kinase (ERK) activation required protein kinase C (PKC) activity, preincubation of H69 cells with the PKCinhibitor GF109203X had no e ect on galanin-dependent ERK activity. A rise of the intracellular calcium concentration was necessary and su cient to mediate galanin-induced ERK activation. In support of G i coupling, stimulation of GALR2 expressed in HEK293 cells inhibited isoproterenol-induced cAMP accumulation and raised cAMP levels in COS-7 cells when coexpressed with a chimeric Ga S -Ga i protein. In H69 cells, galanin activated the monomeric GTPase RhoA and induced stress ®ber formation in Swiss 3T3 cells expressing GALR2. Thus, we provide the ®rst direct evidence that in SCLC the mitogenic neuropeptide galanin, interacting with GALR2, simultaneously activates multiple classes of G proteins and signals through the G q phospholipase C/calcium sequence and a G 12 /Rho pathway. Oncogene (2000) 19, 4199 ± 4209.

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“…Thus, in cell types such as CHO, it has been observed that Ga q can activate an ERK-mediated proliferative pathway through a PKC-dependent but Ras-independent mechanism (Figure 1). However, in other cell types such as the rat vascular smooth muscle and NIH3T3 cells, Ga q appear to activate ERK through a novel pathway involving proline-rich tyrosine kinase-2 (Pyk2) and Ras (Lev et al, 1995;Bourne, 1995). This pathway appears to be activated by the IP 3 generated by the activation of PLC.…”

Section: Ga Q the Conditional Oncogenementioning

confidence: 99%

Regulation of cell proliferation by G proteins

Dhanasekaran

Tsim²,

Dermott³

et al. 1998

Oncogene

136

107

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G Proteins provide signal transduction mechanisms to seven transmembrane receptors. Recent studies have indicated that the a-subunits as well as the bg-subunits of these proteins regulate several critical signaling pathways involved in cell proliferation, di erentiation and apoptosis. Of the 17 a-subunits that have been cloned, at least ten of them have been shown to couple mitogenic signaling in ®broblast cells. Activating mutations in Ga s , Ga i2 , and Ga 12 have been correlated with di erent types of tumors. In addition, the ability of the bg-subunits to activate mitogenic pathways in di erent cell-types has been de®ned. The present review brie¯y summarizes the diverse and novel signaling pathways regulated by the a-as well as the bg-subunits of G proteins in regulating cell proliferation.

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Protein tyrosine kinase PYK2 involved in Ca2+-induced regulation of ion channel and MAP kinase functions

Cited by 1,319 publications

References 45 publications

ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells

ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells

The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to Gq, Gi and G12 proteins

Regulation of cell proliferation by G proteins

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