Cytoskeleton-dependent Tyrosine Phosphorylation of the p130Cas Family Member HEF1 Downstream of the G Protein-coupled Calcitonin Receptor

Zhang, Zhiyuan; Hernandez-Lagunas, Laura; Horne, William C.; Baron, Roland

doi:10.1074/jbc.274.35.25093

Cited by 48 publications

(39 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…41,42 PC-3M cells were grown in chamber slides, serumstarved and treated with 50 nM CT for various times (0-60 min). The cells were then processed for uPA-paxillin double immunofluorescence.…”

Section: Effect Of Ct On Redistribution Of Upa In Focal Adhesion Sitesmentioning

confidence: 99%

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Sabbisetti

Chigurupati

Thomas

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several folds higher than that in benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation increases invasiveness of prostate cancer (PC) cells via activation of protein kinase A. Since the role of urokinase-type plasminogen activator (uPA) in invasion of PC has been established, we tested the hypothesis that CT increases invasion of PC cells by stimulating uPA secretion from PC cells. Exogenously added CT stimulated the secretion of uPA from PC-3M cells in a dose-dependent manner, which was blocked by Rp.cAMP, a competitive inhibitor of protein kinase A. CT stimulated the secretion of MMP-2 and MMP-9 from PC-3M cells, and also increased their invasiveness. Both these actions of CT were blocked by uPA-neutralizing antibodies. Immunofluorescence studies with PC-3M cells suggest that CT stimulated redistribution of cellular uPA to focal adhesion sites, which was further confirmed by co-immunoprecipitation of uPA with focal adhesion kinase (FAK) in response to CT. These results suggest that CT increases invasiveness of PC cells by stimulating PKA-mediated uPA secretion and by redirecting the secreted uPA to focal adhesion sites. The results also suggest that uPA may, at least in part, mediate proinvasive actions of CT on PC cells by stimulating the secretion of gelatinases and degradation of focal adhesion sites. ' 2005 Wiley-Liss, Inc.

show abstract

Section: Effect Of Ct On Redistribution Of Upa In Focal Adhesion Sitesmentioning

confidence: 99%

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Sabbisetti

Chigurupati

Thomas

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Subsequently, the phosphorylated Cas-L regulates several signals involved in cell motility (11)(12)(13) and cell adhesion (14) as a downstream effecter of focal adhesion kinase. In addition, Cas-L functions as a signal transducer of TCR (12,15,16), BCR (17), and G protein-coupled calcitonin receptor (18). The biological functions of Cas-L in lymphocytes, however, remain to be determined.…”

mentioning

confidence: 99%

Crk-Associated Substrate Lymphocyte Type Is Required for Lymphocyte Trafficking and Marginal Zone B Cell Maintenance

Seo¹,

Asai²,

Saito³

et al. 2005

The Journal of Immunology

111

View full text Add to dashboard Cite

The lymphocyte-specific Cas family protein Cas-L (Crk-associated substrate lymphocyte type) has been implicated to function in lymphocyte movement, mediated mainly by integrin signaling. However, its physiological role is poorly understood. In this study we analyzed the function of Cas-L in lymphocytes using gene-targeted mice. The mutant mice showed a deficit of marginal zone B (MZB) cells and a decrease of cell number in secondary lymphoid organs. An insufficient chemotactic response and perturbed cell adhesion were observed in Cas-L-deficient lymphocytes, suggesting that the aberrant localization was responsible for the deficit of MZB cells. Moreover, we found that lymphocyte trafficking was altered in Cas-L-deficient mice, which gave a potential reason for contraction of secondary lymphoid tissues. Thus, Cas-L affects homeostasis of MZB cells and peripheral lymphoid organs, which is considered to be relevant to impaired lymphocyte migration and adhesion.

show abstract

“…In addition, hItch can be recruited by the latent membrane protein 2A of Epstein-Barr virus to mediate the ubiquitination and degradation of Lyn and Syk kinase, thus down-regulating B cell signaling (32). Our studies reported here demonstrate a new role of AIP4/hItch as a ubiquitin E3 ligase for the multidomain docking protein HEF1, which has been implicated to function as an adapter protein in many signaling pathways such as those of integrin, T cell antigen receptor, and B cell antigen receptor (10,(12)(13)(14)(15). In our previous studies, HEF1 was also found to be involved in TGF-␤ signaling pathways, by interacting with Smad3, a key signal transducer in the TGF-␤ signaling pathway (7).…”

Section: Discussionmentioning

confidence: 71%

“…5C, lanes 10 -12). To test whether the ligase activity of AIP4 is necessary for such an ability of AIP4, the in vitro translated AIP4CA was added to the reaction system, as shown in lanes [13][14][15]. The ligase-dead mutant completely failed in inducing HEF1 degradation.…”

Section: The Ligase Activity Of Aip4 Is Essential For Aip4-induced Hementioning

confidence: 99%

“…The expression of HEF1 is cell cycle-regulated, with p105 HEF1 and p115 HEF1 accumulating at the focal adhesion sites when cells go through S and G 2 phase, whereas p55 HEF1 is specifically produced and localized to the mitotic spindle during mitosis (8). So far, HEF1 has been implicated in integrin, T cell antigen receptor, B cell antigen receptor, and the G-protein coupled calcitonin receptor signaling pathways (10,(12)(13)(14)(15). Molecular and genetic studies indicated that HEF1 overexpression leads to an increase in cell motility and apoptosis, consistent with a role of HEF1 in regulating integrin signaling (16 -19).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Atrophin-1-interacting Protein 4/Human Itch Is a Ubiquitin E3 Ligase for Human Enhancer of Filamentation 1 in Transforming Growth Factor-β Signaling Pathways

Guedes

Wang

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Atrophin-1-interacting protein 4 (AIP4) is the human homolog of the mouse Itch protein (hItch), an E3 ligase for Notch and JunB. Human enhancer of filamentation 1 (HEF1) has been implicated in signaling pathways such as those mediated by integrin, T cell receptor, and B cell receptor and functions as a multidomain docking protein. Recent studies suggest that HEF1 is also involved in the transforming growth factor-␤ (TGF-␤) signaling pathways, by interacting with Smad3, a key signal transducer downstream of the TGF-␤ type I receptor. The interaction of Smad3 with HEF1 induces HEF1 proteasomal degradation, which was further enhanced by TGF-␤ stimulation. The detailed molecular mechanisms of HEF1 degradation regulated by Smad3 were poorly understood. Here we report our studies that demonstrate the function of AIP4 as an ubiquitin E3 ligase for HEF1. AIP4 forms a complex with both Smad3 and HEF1 through its WW domains in a TGF-␤-independent manner and regulates HEF1 ubiquitination and degradation, which can be enhanced by TGF-␤ stimulation. These findings reveal a new mechanism for Smad3-regulated proteasomal degradation events and also broaden the network of cross-talk between the TGF-␤ signaling pathway and those involving HEF1 and AIP4.The transforming growth factor-␤ (TGF-␤) 1 signaling is involved in a broad range of cellular functions, including proliferation, adhesion, apoptosis, differentiation, and specification of developmental fate (1, 2). The extracellular signals were transduced to the nucleus by the sequential association of type II and type I receptors and the Smad protein cascades (3, 4). The binding of ligands to the receptors leads to the phosphorylation of Smad2 and Smad3 at their SSXS motif within the COOH termini. The phosphorylated Smad2 or Smad3 forms complexes with Smad4 and translocates into the nucleus, where they function as DNA-binding transcription factors. Recently, Smad3 was discovered to have the novel ability of regulating the proteasomal degradation of the nuclear proto-oncoproteins SnoN and Ski (5, 6) as well as the human enhancer of filmentation 1 (HEF1) (7).HEF1 is a member of a multiple domain docking protein Cas family including p130 cas and Efs that have been implicated as signaling mediators of diverse processes including cellular attachment, motility, growth factor responses, apoptosis, and oncogenic transformation (8). HEF1 was first isolated in a screen for human proteins with the ability to alter Saccharomyces cerevisiae morphology from round to filamentous hyperpolarized cells (9). Based upon its homology to p130 cas , another group independently isolated HEF1, named Cas-L (10). Members of this family share similar domains, with an aminoterminal Src homology 3 domain that binds polyproline-containing protein, a large central domain encompassing multiple tyrosine motifs that are recognized by the Src homology 2 domain protein upon phosphorylation, a serine-rich domain, and a carboxyl-terminal domain containing a helix-loop-helix motif (9, 11).Earlier studies have showed t...

show abstract

Cytoskeleton-dependent Tyrosine Phosphorylation of the p130Cas Family Member HEF1 Downstream of the G Protein-coupled Calcitonin Receptor

Cited by 48 publications

References 52 publications

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Crk-Associated Substrate Lymphocyte Type Is Required for Lymphocyte Trafficking and Marginal Zone B Cell Maintenance

Atrophin-1-interacting Protein 4/Human Itch Is a Ubiquitin E3 Ligase for Human Enhancer of Filamentation 1 in Transforming Growth Factor-β Signaling Pathways

Contact Info

Product

Resources

About