Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals

Rosa Lapalombella; Yuh Ying Yeh; Liwen Wang; Asha Ramanunni; Sarwish Rafiq; Shruti Jha; Justin Staubli; David M. Lucas; Rajeswaran Mani; Sarah E.M. Herman; Amy J. Johnson; Arletta Lozanski; Leslie Andritsos; Jeffrey Jones; Joseph M. Flynn; Brian Lannutti; Peter Thompson; Paul Algate; Scott Stromatt; David Jarjoura; Xiaokui Mo; Dasheng Wang; Ching Shih Chen; Gerard Lozanski; Nyla A. Heerema; Susheela Tridandapani; Michael A. Freitas; Natarajan Muthusamy; John C. Byrd

doi:10.1016/j.ccr.2012.03.040

Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals

Rosa Lapalombella, Yuh Ying Yeh, Liwen Wang, Asha Ramanunni, Sarwish Rafiq, Shruti Jha, Justin Staubli, David M. Lucas, Rajeswaran Mani, Sarah E.M. Herman, Amy J. Johnson, Arletta Lozanski, Leslie Andritsos, Jeffrey Jones, Joseph M. Flynn, Brian Lannutti, Peter Thompson, Paul Algate, Scott Stromatt, David JarjouraXiaokui Mo, Dasheng Wang, Ching Shih Chen, Gerard Lozanski, Nyla A. Heerema, Susheela Tridandapani, Michael A. Freitas, Natarajan Muthusamy, John C. Byrd

Huck Institutes of the Life Sciences

Research output: Contribution to journal › Article › peer-review

122 Scopus citations

Abstract

Tetraspanins are commonly believed to act only as "molecular facilitators," with no direct role in signal transduction. We herein demonstrate that upon ligation, CD37, a tetraspanin molecule expressed on mature normal and transformed B cells, becomes tyrosine phosphorylated, associates with proximal signaling molecules, and initiates a cascade of events leading to apoptosis. Moreover, we have identified two tyrosine residues with opposing regulatory functions: one lies in the N-terminal domain of CD37 in a predicted "ITIM-like" motif and mediates SHP1-dependent death, whereas the second lies in a predicted "ITAM motif" in the C-terminal domain of CD37 and counteracts death signals by mediating phosphatidylinositol 3-kinase-dependent survival.

Original language	English (US)
Pages (from-to)	694-708
Number of pages	15
Journal	Cancer Cell
Volume	21
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2012.03.040
State	Published - May 25 2012

All Science Journal Classification (ASJC) codes

Oncology
Cell Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2012.03.040

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Lapalombella, R., Yeh, Y. Y., Wang, L., Ramanunni, A., Rafiq, S., Jha, S., Staubli, J., Lucas, D. M., Mani, R., Herman, S. E. M., Johnson, A. J., Lozanski, A., Andritsos, L., Jones, J., Flynn, J. M., Lannutti, B., Thompson, P., Algate, P., Stromatt, S., ... Byrd, J. C. (2012). Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals. Cancer Cell, 21(5), 694-708. https://doi.org/10.1016/j.ccr.2012.03.040

@article{7c80f6955a934ed6b39d3ede819b55e2,

title = "Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals",

abstract = "Tetraspanins are commonly believed to act only as {"}molecular facilitators,{"} with no direct role in signal transduction. We herein demonstrate that upon ligation, CD37, a tetraspanin molecule expressed on mature normal and transformed B cells, becomes tyrosine phosphorylated, associates with proximal signaling molecules, and initiates a cascade of events leading to apoptosis. Moreover, we have identified two tyrosine residues with opposing regulatory functions: one lies in the N-terminal domain of CD37 in a predicted {"}ITIM-like{"} motif and mediates SHP1-dependent death, whereas the second lies in a predicted {"}ITAM motif{"} in the C-terminal domain of CD37 and counteracts death signals by mediating phosphatidylinositol 3-kinase-dependent survival.",

author = "Rosa Lapalombella and Yeh, {Yuh Ying} and Liwen Wang and Asha Ramanunni and Sarwish Rafiq and Shruti Jha and Justin Staubli and Lucas, {David M.} and Rajeswaran Mani and Herman, {Sarah E.M.} and Johnson, {Amy J.} and Arletta Lozanski and Leslie Andritsos and Jeffrey Jones and Flynn, {Joseph M.} and Brian Lannutti and Peter Thompson and Paul Algate and Scott Stromatt and David Jarjoura and Xiaokui Mo and Dasheng Wang and Chen, {Ching Shih} and Gerard Lozanski and Heerema, {Nyla A.} and Susheela Tridandapani and Freitas, {Michael A.} and Natarajan Muthusamy and Byrd, {John C.}",

note = "Funding Information: We thank the members of the CLL Experimental Therapeutics laboratory, Freitas laboratory, and Dr. Guido Marcucci, for critical comments and review of the final manuscript, and Dr. Shu-Huei Wang for BIM promoter reporter plasmids. We are grateful for research support from The Leukemia and Lymphoma Society and the National Cancer Institute (grants P50 CA140158, PO1 CA95426, PO1 CA81534, 1K12 CA133250, and RO1 CA107106). Mr. and Mrs. Michael Thomas, The Harry Mangurian Foundation, and The D. Warren Brown Foundation also supported this work. ",

year = "2012",

month = may,

day = "25",

doi = "10.1016/j.ccr.2012.03.040",

language = "English (US)",

volume = "21",

pages = "694--708",

journal = "Cancer Cell",

issn = "1535-6108",

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Lapalombella, R, Yeh, YY, Wang, L, Ramanunni, A, Rafiq, S, Jha, S, Staubli, J, Lucas, DM, Mani, R, Herman, SEM, Johnson, AJ, Lozanski, A, Andritsos, L, Jones, J, Flynn, JM, Lannutti, B, Thompson, P, Algate, P, Stromatt, S, Jarjoura, D, Mo, X, Wang, D, Chen, CS, Lozanski, G, Heerema, NA, Tridandapani, S, Freitas, MA, Muthusamy, N & Byrd, JC 2012, 'Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals', Cancer Cell, vol. 21, no. 5, pp. 694-708. https://doi.org/10.1016/j.ccr.2012.03.040

TY - JOUR

T1 - Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals

AU - Lapalombella, Rosa

AU - Yeh, Yuh Ying

AU - Wang, Liwen

AU - Ramanunni, Asha

AU - Rafiq, Sarwish

AU - Jha, Shruti

AU - Staubli, Justin

AU - Lucas, David M.

AU - Mani, Rajeswaran

AU - Herman, Sarah E.M.

AU - Johnson, Amy J.

AU - Lozanski, Arletta

AU - Andritsos, Leslie

AU - Jones, Jeffrey

AU - Flynn, Joseph M.

AU - Lannutti, Brian

AU - Thompson, Peter

AU - Algate, Paul

AU - Stromatt, Scott

AU - Jarjoura, David

AU - Mo, Xiaokui

AU - Wang, Dasheng

AU - Chen, Ching Shih

AU - Lozanski, Gerard

AU - Heerema, Nyla A.

AU - Tridandapani, Susheela

AU - Freitas, Michael A.

AU - Muthusamy, Natarajan

AU - Byrd, John C.

N1 - Funding Information: We thank the members of the CLL Experimental Therapeutics laboratory, Freitas laboratory, and Dr. Guido Marcucci, for critical comments and review of the final manuscript, and Dr. Shu-Huei Wang for BIM promoter reporter plasmids. We are grateful for research support from The Leukemia and Lymphoma Society and the National Cancer Institute (grants P50 CA140158, PO1 CA95426, PO1 CA81534, 1K12 CA133250, and RO1 CA107106). Mr. and Mrs. Michael Thomas, The Harry Mangurian Foundation, and The D. Warren Brown Foundation also supported this work.

PY - 2012/5/25

Y1 - 2012/5/25

N2 - Tetraspanins are commonly believed to act only as "molecular facilitators," with no direct role in signal transduction. We herein demonstrate that upon ligation, CD37, a tetraspanin molecule expressed on mature normal and transformed B cells, becomes tyrosine phosphorylated, associates with proximal signaling molecules, and initiates a cascade of events leading to apoptosis. Moreover, we have identified two tyrosine residues with opposing regulatory functions: one lies in the N-terminal domain of CD37 in a predicted "ITIM-like" motif and mediates SHP1-dependent death, whereas the second lies in a predicted "ITAM motif" in the C-terminal domain of CD37 and counteracts death signals by mediating phosphatidylinositol 3-kinase-dependent survival.

AB - Tetraspanins are commonly believed to act only as "molecular facilitators," with no direct role in signal transduction. We herein demonstrate that upon ligation, CD37, a tetraspanin molecule expressed on mature normal and transformed B cells, becomes tyrosine phosphorylated, associates with proximal signaling molecules, and initiates a cascade of events leading to apoptosis. Moreover, we have identified two tyrosine residues with opposing regulatory functions: one lies in the N-terminal domain of CD37 in a predicted "ITIM-like" motif and mediates SHP1-dependent death, whereas the second lies in a predicted "ITAM motif" in the C-terminal domain of CD37 and counteracts death signals by mediating phosphatidylinositol 3-kinase-dependent survival.

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UR - http://www.scopus.com/inward/citedby.url?scp=84861415717&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2012.03.040

DO - 10.1016/j.ccr.2012.03.040

M3 - Article

C2 - 22624718

AN - SCOPUS:84861415717

SN - 1535-6108

VL - 21

SP - 694

EP - 708

JO - Cancer Cell

JF - Cancer Cell

IS - 5

ER -

Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals

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