Pseudopodium-enriched atypical kinase 1 regulates the cytoskeleton and cancer progression

Yingchun Wang; Jonathan A. Kelber; Hop S.Tran Cao; Greg T. Cantin; Rui Lin; Wei Wang; Sharmeela Kaushal; Jeanne M. Bristow; Thomas S. Edgington; Robert M. Hoffman; Michael Bouvet; John R. Yates; Richard L. Klemke

doi:10.1073/pnas.0914776107

Pseudopodium-enriched atypical kinase 1 regulates the cytoskeleton and cancer progression

Yingchun Wang, Jonathan A. Kelber, Hop S.Tran Cao, Greg T. Cantin, Rui Lin, Wei Wang, Sharmeela Kaushal, Jeanne M. Bristow, Thomas S. Edgington, Robert M. Hoffman, Michael Bouvet, John R. Yates, Richard L. Klemke

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

84 Scopus citations

Abstract

Regulationof the actin-myosin cytoskeletonplays a central role incell migration and cancer progression. Here, we report the discovery of a cytoskeleton-associated kinase, pseudopodium-enriched atypical kinase 1 (PEAK1). PEAK1 is a 190-kDa nonreceptor tyrosine kinase that localizes to actin filaments and focal adhesions. PEAK1 undergoes Src-induced tyrosine phosphorylation, regulates the p130Cas-Crk-paxillin and Erk signaling pathways, and operates downstream of integrin and epidermal growth factor receptors (EGFR) to control cell spreading, migration, and proliferation. Perturbation of PEAK1 levels in cancer cells alters anchorage-independent growth and tumor progression in mice. Notably, primary and metastatic samples from colon cancer patients display amplified PEAK1 levels in 81% of the cases. Our findings indicate that PEAK1 is an important cytoskeletal regulatory kinase and possible target for anticancer therapy.

Original language	English (US)
Pages (from-to)	10920-10925
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	107
Issue number	24
DOIs	https://doi.org/10.1073/pnas.0914776107
State	Published - Jun 15 2010
Externally published	Yes

Keywords

Cancer
Cell migration
Phosphoproteomics

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.0914776107

Cite this

Wang, Y., Kelber, J. A., Cao, H. S. T., Cantin, G. T., Lin, R., Wang, W., Kaushal, S., Bristow, J. M., Edgington, T. S., Hoffman, R. M., Bouvet, M., Yates, J. R., & Klemke, R. L. (2010). Pseudopodium-enriched atypical kinase 1 regulates the cytoskeleton and cancer progression. Proceedings of the National Academy of Sciences of the United States of America, 107(24), 10920-10925. https://doi.org/10.1073/pnas.0914776107

Wang, Y, Kelber, JA, Cao, HST, Cantin, GT, Lin, R, Wang, W, Kaushal, S, Bristow, JM, Edgington, TS, Hoffman, RM, Bouvet, M, Yates, JR & Klemke, RL 2010, 'Pseudopodium-enriched atypical kinase 1 regulates the cytoskeleton and cancer progression', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 24, pp. 10920-10925. https://doi.org/10.1073/pnas.0914776107

@article{a433c838b1dc420b9139a12cabc38575,

title = "Pseudopodium-enriched atypical kinase 1 regulates the cytoskeleton and cancer progression",

abstract = "Regulationof the actin-myosin cytoskeletonplays a central role incell migration and cancer progression. Here, we report the discovery of a cytoskeleton-associated kinase, pseudopodium-enriched atypical kinase 1 (PEAK1). PEAK1 is a 190-kDa nonreceptor tyrosine kinase that localizes to actin filaments and focal adhesions. PEAK1 undergoes Src-induced tyrosine phosphorylation, regulates the p130Cas-Crk-paxillin and Erk signaling pathways, and operates downstream of integrin and epidermal growth factor receptors (EGFR) to control cell spreading, migration, and proliferation. Perturbation of PEAK1 levels in cancer cells alters anchorage-independent growth and tumor progression in mice. Notably, primary and metastatic samples from colon cancer patients display amplified PEAK1 levels in 81% of the cases. Our findings indicate that PEAK1 is an important cytoskeletal regulatory kinase and possible target for anticancer therapy.",

keywords = "Cancer, Cell migration, Phosphoproteomics",

author = "Yingchun Wang and Kelber, {Jonathan A.} and Cao, {Hop S.Tran} and Cantin, {Greg T.} and Rui Lin and Wei Wang and Sharmeela Kaushal and Bristow, {Jeanne M.} and Edgington, {Thomas S.} and Hoffman, {Robert M.} and Michael Bouvet and Yates, {John R.} and Klemke, {Richard L.}",

year = "2010",

month = jun,

day = "15",

doi = "10.1073/pnas.0914776107",

language = "English (US)",

volume = "107",

pages = "10920--10925",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "24",

}

TY - JOUR

T1 - Pseudopodium-enriched atypical kinase 1 regulates the cytoskeleton and cancer progression

AU - Wang, Yingchun

AU - Kelber, Jonathan A.

AU - Cao, Hop S.Tran

AU - Cantin, Greg T.

AU - Lin, Rui

AU - Wang, Wei

AU - Kaushal, Sharmeela

AU - Bristow, Jeanne M.

AU - Edgington, Thomas S.

AU - Hoffman, Robert M.

AU - Bouvet, Michael

AU - Yates, John R.

AU - Klemke, Richard L.

PY - 2010/6/15

Y1 - 2010/6/15

N2 - Regulationof the actin-myosin cytoskeletonplays a central role incell migration and cancer progression. Here, we report the discovery of a cytoskeleton-associated kinase, pseudopodium-enriched atypical kinase 1 (PEAK1). PEAK1 is a 190-kDa nonreceptor tyrosine kinase that localizes to actin filaments and focal adhesions. PEAK1 undergoes Src-induced tyrosine phosphorylation, regulates the p130Cas-Crk-paxillin and Erk signaling pathways, and operates downstream of integrin and epidermal growth factor receptors (EGFR) to control cell spreading, migration, and proliferation. Perturbation of PEAK1 levels in cancer cells alters anchorage-independent growth and tumor progression in mice. Notably, primary and metastatic samples from colon cancer patients display amplified PEAK1 levels in 81% of the cases. Our findings indicate that PEAK1 is an important cytoskeletal regulatory kinase and possible target for anticancer therapy.

AB - Regulationof the actin-myosin cytoskeletonplays a central role incell migration and cancer progression. Here, we report the discovery of a cytoskeleton-associated kinase, pseudopodium-enriched atypical kinase 1 (PEAK1). PEAK1 is a 190-kDa nonreceptor tyrosine kinase that localizes to actin filaments and focal adhesions. PEAK1 undergoes Src-induced tyrosine phosphorylation, regulates the p130Cas-Crk-paxillin and Erk signaling pathways, and operates downstream of integrin and epidermal growth factor receptors (EGFR) to control cell spreading, migration, and proliferation. Perturbation of PEAK1 levels in cancer cells alters anchorage-independent growth and tumor progression in mice. Notably, primary and metastatic samples from colon cancer patients display amplified PEAK1 levels in 81% of the cases. Our findings indicate that PEAK1 is an important cytoskeletal regulatory kinase and possible target for anticancer therapy.

KW - Cancer

KW - Cell migration

KW - Phosphoproteomics

UR - http://www.scopus.com/inward/record.url?scp=77954643220&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954643220&partnerID=8YFLogxK

U2 - 10.1073/pnas.0914776107

DO - 10.1073/pnas.0914776107

M3 - Article

C2 - 20534451

AN - SCOPUS:77954643220

SN - 0027-8424

VL - 107

SP - 10920

EP - 10925

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 24

ER -

Pseudopodium-enriched atypical kinase 1 regulates the cytoskeleton and cancer progression

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this