Association of an 80 kda protein with c-cam1 cytoplasmic domain correlates with c-cam1-mediated growth inhibition

Association of an 80 kda protein with c-cam1 cytoplasmic domain correlates with c-cam1-mediated growth inhibition

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ABSTRACT Decreased expression of C-CAM, a member of the CEA family of immunoglobulin like cell adhesion molecules, occurs in carcinomas of the colon, liver and prostate. Down regulation of C-CAM during the early stages of carcinogenesis in rat liver and human prostate has also been reported. We have recently shown that restoration of the expression of the isoform with long cytoplasmic domain, C-CAM1, leads to suppression of the tumorigenicity of prostatic carcinoma cells _IN VIVO_ and growth suppression _IN VITRO_. These observations suggest that C-CAM1 may play an important role in regulating cell growth in normal tissues. Previous studies have demonstrated that the function of many members of the Ig-supergene family is dependent on interactions with cytoplasmic proteins. In the present study, we have used a bifunctional cross-linker to identify cellular proteins that interact directly with C-CAM1. Immunoblot analysis of WGA bound membrane proteins crosslinked with DSS identified a 180 kDa complex composed of C-CAM and an 80 kDa protein designated CAP-80 (_C_-CAM _A_ssociated _P_rotein). Immunoprecipitation with anti-C-CAM antibodies showed that CAP-80 was co-precipitated with C-CAM from detergent solubilized, WGA-purified proteins. To assess the specificity of CAP-80 binding, the ability of CAP-80 to form stable complexes with C-CAM1 mutants expressed in insect cells was tested. Deletion of the cytoplasmic domain of C-CAM1 abolished complex formation whereas deletion of the extracellular Ig domains had no effect. These results suggest that a CAP-80 homologue (ICAP-80) is present in insect cells and ICAP-80 interacts with the cytoplasmic domain of C-CAM1. Replacement of Tyr488, a residue in the cytoplasmic domain known to be phosphorylated _IN VIVO_, with Phe did not diminish the association between C-CAM1 and ICAP-80, suggesting that Tyr488 phosphorylation is not required for association. The ability of various C-CAM1 mutants to associate with ICAP-80 correlated with their growth inhibitory activities, suggesting that ICAP-80/CAP-80 may play an important role in C-CAM1-mediated growth inhibition. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS HMGB2-INDUCED CALRETICULIN TRANSLOCATION REQUIRED FOR IMMUNOGENIC CELL DEATH AND FERROPTOSIS OF CANCER CELLS ARE CONTROLLED BY THE NUCLEAR EXPORTER XPO1 Article Open access 01 October 2024 TROP-2, NA+/K+ ATPASE, CD9, PKCΑ, COFILIN ASSEMBLE A MEMBRANE SIGNALING SUPER-COMPLEX THAT DRIVES COLORECTAL CANCER GROWTH AND INVASION Article 07 February 2022 CAMTA1–PPP3CA–NFATC4 MULTI-PROTEIN COMPLEX MEDIATES THE RESISTANCE OF COLORECTAL CANCER TO OXALIPLATIN Article Open access 24 March 2022 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA Weiping Luo, Karen Earley, Vicky Tantingco & Sue-Hwa Lin * Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA Sue-Hwa Lin * Department of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island, 02903, USA Douglas C Hixson * Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, 77030, Texas, USA T Chyau Liang Authors * Weiping Luo View author publications You can also search for this author inPubMed Google Scholar * Karen Earley View author publications You can also search for this author inPubMed Google Scholar * Vicky Tantingco View author publications You can also search for this author inPubMed Google Scholar * Douglas C Hixson View author publications You can also search for this author inPubMed Google Scholar * T Chyau Liang View author publications You can also search for this author inPubMed Google Scholar * Sue-Hwa Lin View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Luo, W., Earley, K., Tantingco, V. _et al._ Association of an 80 kDa protein with C-CAM1 cytoplasmic domain correlates with C-CAM1-mediated growth inhibition. _Oncogene_ 16, 1141–1147 (1998). https://doi.org/10.1038/sj.onc.1201619 Download citation * Received: 02 July 1997 * Revised: 03 October 1997 * Accepted: 03 October 1997 * Published: 10 March 1998 * Issue Date: 05 March 1998 * DOI: https://doi.org/10.1038/sj.onc.1201619 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * cell adhesion molecule * tumor suppressor * cross linker * associated protein

ABSTRACT Decreased expression of C-CAM, a member of the CEA family of immunoglobulin like cell adhesion molecules, occurs in carcinomas of the colon, liver and prostate. Down regulation of


C-CAM during the early stages of carcinogenesis in rat liver and human prostate has also been reported. We have recently shown that restoration of the expression of the isoform with long


cytoplasmic domain, C-CAM1, leads to suppression of the tumorigenicity of prostatic carcinoma cells _IN VIVO_ and growth suppression _IN VITRO_. These observations suggest that C-CAM1 may


play an important role in regulating cell growth in normal tissues. Previous studies have demonstrated that the function of many members of the Ig-supergene family is dependent on


interactions with cytoplasmic proteins. In the present study, we have used a bifunctional cross-linker to identify cellular proteins that interact directly with C-CAM1. Immunoblot analysis


of WGA bound membrane proteins crosslinked with DSS identified a 180 kDa complex composed of C-CAM and an 80 kDa protein designated CAP-80 (_C_-CAM _A_ssociated _P_rotein).


Immunoprecipitation with anti-C-CAM antibodies showed that CAP-80 was co-precipitated with C-CAM from detergent solubilized, WGA-purified proteins. To assess the specificity of CAP-80


binding, the ability of CAP-80 to form stable complexes with C-CAM1 mutants expressed in insect cells was tested. Deletion of the cytoplasmic domain of C-CAM1 abolished complex formation


whereas deletion of the extracellular Ig domains had no effect. These results suggest that a CAP-80 homologue (ICAP-80) is present in insect cells and ICAP-80 interacts with the cytoplasmic


domain of C-CAM1. Replacement of Tyr488, a residue in the cytoplasmic domain known to be phosphorylated _IN VIVO_, with Phe did not diminish the association between C-CAM1 and ICAP-80,


suggesting that Tyr488 phosphorylation is not required for association. The ability of various C-CAM1 mutants to associate with ICAP-80 correlated with their growth inhibitory activities,


suggesting that ICAP-80/CAP-80 may play an important role in C-CAM1-mediated growth inhibition. Access through your institution Buy or subscribe This is a preview of subscription content,


access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn


more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS


OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS HMGB2-INDUCED CALRETICULIN TRANSLOCATION


REQUIRED FOR IMMUNOGENIC CELL DEATH AND FERROPTOSIS OF CANCER CELLS ARE CONTROLLED BY THE NUCLEAR EXPORTER XPO1 Article Open access 01 October 2024 TROP-2, NA+/K+ ATPASE, CD9, PKCΑ, COFILIN


ASSEMBLE A MEMBRANE SIGNALING SUPER-COMPLEX THAT DRIVES COLORECTAL CANCER GROWTH AND INVASION Article 07 February 2022 CAMTA1–PPP3CA–NFATC4 MULTI-PROTEIN COMPLEX MEDIATES THE RESISTANCE OF


COLORECTAL CANCER TO OXALIPLATIN Article Open access 24 March 2022 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Molecular Pathology, The University of Texas MD Anderson Cancer


Center, Houston, 77030, Texas, USA Weiping Luo, Karen Earley, Vicky Tantingco & Sue-Hwa Lin * Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer


Center, Houston, 77030, Texas, USA Sue-Hwa Lin * Department of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island, 02903, USA Douglas C Hixson * Department


of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, 77030, Texas, USA T Chyau Liang Authors * Weiping Luo View author publications You can also


search for this author inPubMed Google Scholar * Karen Earley View author publications You can also search for this author inPubMed Google Scholar * Vicky Tantingco View author publications


You can also search for this author inPubMed Google Scholar * Douglas C Hixson View author publications You can also search for this author inPubMed Google Scholar * T Chyau Liang View


author publications You can also search for this author inPubMed Google Scholar * Sue-Hwa Lin View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND


PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Luo, W., Earley, K., Tantingco, V. _et al._ Association of an 80 kDa protein with C-CAM1 cytoplasmic domain


correlates with C-CAM1-mediated growth inhibition. _Oncogene_ 16, 1141–1147 (1998). https://doi.org/10.1038/sj.onc.1201619 Download citation * Received: 02 July 1997 * Revised: 03 October


1997 * Accepted: 03 October 1997 * Published: 10 March 1998 * Issue Date: 05 March 1998 * DOI: https://doi.org/10.1038/sj.onc.1201619 SHARE THIS ARTICLE Anyone you share the following link


with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt


content-sharing initiative KEYWORDS * cell adhesion molecule * tumor suppressor * cross linker * associated protein