Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix

Joel B Heim; Edwin J Squirewell; Ancilla Neu; Georg Zocher; Sindhuja Sominidi-Damodaran; Saranya P Wyles; Ekaterina Nikolova; Nille Behrendt; Ditte M Saunte; Jorgen Lock-Andersen; Krutika S Gaonkar; Huihuang Yan; Jann N Sarkaria; Mira Krendel; Jan van Deursen; Remco Sprangers; Thilo Stehle; Ralph T Böttcher; Jeong-Heon Lee; Tamas Ordog; Alexander Meves

doi:10.1073/pnas.1614894114

Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix

Joel B Heim, Edwin J Squirewell, Ancilla Neu, Georg Zocher, Sindhuja Sominidi-Damodaran, Saranya P Wyles, Ekaterina Nikolova, Nille Behrendt, Ditte M Saunte, Jorgen Lock-Andersen, Krutika S Gaonkar, Huihuang Yan, Jann N Sarkaria, Mira Krendel, Jan van Deursen, Remco Sprangers, Thilo Stehle, Ralph T Böttcher, Jeong-Heon Lee, Tamas OrdogAlexander Meves

Institut for Klinisk Medicin

10 Citationer (Scopus)

Abstract

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required for in vivo FAK function until late midgestation. Here, we directly tested this hypothesis by generating mice with FAK Y397-to-phenylalanine (F) mutations in the germline. We found that Y397F embryos exhibited reduced mesodermal fibronectin (FN) and osteopontin expression and died during mesoderm development akin to FAK kinase-dead mice. We identified myosin-1E (MYO1E), an actin-dependent molecular motor, to interact directly with the FAK FERM-kinase linker and induce FAK kinase activity and Y397 phosphorylation. Active FAK in turn accumulated in the nucleus where it led to the expression of osteopontin and other FN-type matrix in both mouse embryonic fibroblasts and human melanoma. Our data support a model in which FAK Y397 autophosphorylation is required for FAK function in vivo and is positively regulated by MYO1E.

Originalsprog	Engelsk
Tidsskrift	Proceedings of the National Academy of Sciences of the United States of America
Vol/bind	114
Udgave nummer	15
Sider (fra-til)	3933-3938
ISSN	0027-8424
DOI	https://doi.org/10.1073/pnas.1614894114
Status	Udgivet - 11 apr. 2017

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1073/pnas.1614894114

3933.full.pdfForlagets udgivne version, 1,54 MB

http://europepmc.org/articles/pmc5393228?pdf=renderLicens: Andet

Citationsformater

Heim, J. B., Squirewell, E. J., Neu, A., Zocher, G., Sominidi-Damodaran, S., Wyles, S. P., Nikolova, E., Behrendt, N., Saunte, D. M., Lock-Andersen, J., Gaonkar, K. S., Yan, H., Sarkaria, J. N., Krendel, M., van Deursen, J., Sprangers, R., Stehle, T., Böttcher, R. T., Lee, J.-H., ... Meves, A. (2017). Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix. Proceedings of the National Academy of Sciences of the United States of America, 114(15), 3933-3938. https://doi.org/10.1073/pnas.1614894114

Heim, JB, Squirewell, EJ, Neu, A, Zocher, G, Sominidi-Damodaran, S, Wyles, SP, Nikolova, E, Behrendt, N, Saunte, DM, Lock-Andersen, J, Gaonkar, KS, Yan, H, Sarkaria, JN, Krendel, M, van Deursen, J, Sprangers, R, Stehle, T, Böttcher, RT, Lee, J-H, Ordog, T & Meves, A 2017, 'Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix', Proceedings of the National Academy of Sciences of the United States of America, bind 114, nr. 15, s. 3933-3938. https://doi.org/10.1073/pnas.1614894114

@article{9a1620d2b3454c45a68ab19ab66b14ff,

title = "Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix",

abstract = "Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required for in vivo FAK function until late midgestation. Here, we directly tested this hypothesis by generating mice with FAK Y397-to-phenylalanine (F) mutations in the germline. We found that Y397F embryos exhibited reduced mesodermal fibronectin (FN) and osteopontin expression and died during mesoderm development akin to FAK kinase-dead mice. We identified myosin-1E (MYO1E), an actin-dependent molecular motor, to interact directly with the FAK FERM-kinase linker and induce FAK kinase activity and Y397 phosphorylation. Active FAK in turn accumulated in the nucleus where it led to the expression of osteopontin and other FN-type matrix in both mouse embryonic fibroblasts and human melanoma. Our data support a model in which FAK Y397 autophosphorylation is required for FAK function in vivo and is positively regulated by MYO1E.",

author = "Heim, {Joel B} and Squirewell, {Edwin J} and Ancilla Neu and Georg Zocher and Sindhuja Sominidi-Damodaran and Wyles, {Saranya P} and Ekaterina Nikolova and Nille Behrendt and Saunte, {Ditte M} and Jorgen Lock-Andersen and Gaonkar, {Krutika S} and Huihuang Yan and Sarkaria, {Jann N} and Mira Krendel and {van Deursen}, Jan and Remco Sprangers and Thilo Stehle and B{\"o}ttcher, {Ralph T} and Jeong-Heon Lee and Tamas Ordog and Alexander Meves",

year = "2017",

month = apr,

day = "11",

doi = "10.1073/pnas.1614894114",

language = "English",

volume = "114",

pages = "3933--3938",

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

issn = "0027-8424",

publisher = "The National Academy of Sciences of the United States of America",

number = "15",

}

TY - JOUR

T1 - Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix

AU - Heim, Joel B

AU - Squirewell, Edwin J

AU - Neu, Ancilla

AU - Zocher, Georg

AU - Sominidi-Damodaran, Sindhuja

AU - Wyles, Saranya P

AU - Nikolova, Ekaterina

AU - Behrendt, Nille

AU - Saunte, Ditte M

AU - Lock-Andersen, Jorgen

AU - Gaonkar, Krutika S

AU - Yan, Huihuang

AU - Sarkaria, Jann N

AU - Krendel, Mira

AU - van Deursen, Jan

AU - Sprangers, Remco

AU - Stehle, Thilo

AU - Böttcher, Ralph T

AU - Lee, Jeong-Heon

AU - Ordog, Tamas

AU - Meves, Alexander

PY - 2017/4/11

Y1 - 2017/4/11

N2 - Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required for in vivo FAK function until late midgestation. Here, we directly tested this hypothesis by generating mice with FAK Y397-to-phenylalanine (F) mutations in the germline. We found that Y397F embryos exhibited reduced mesodermal fibronectin (FN) and osteopontin expression and died during mesoderm development akin to FAK kinase-dead mice. We identified myosin-1E (MYO1E), an actin-dependent molecular motor, to interact directly with the FAK FERM-kinase linker and induce FAK kinase activity and Y397 phosphorylation. Active FAK in turn accumulated in the nucleus where it led to the expression of osteopontin and other FN-type matrix in both mouse embryonic fibroblasts and human melanoma. Our data support a model in which FAK Y397 autophosphorylation is required for FAK function in vivo and is positively regulated by MYO1E.

AB - Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required for in vivo FAK function until late midgestation. Here, we directly tested this hypothesis by generating mice with FAK Y397-to-phenylalanine (F) mutations in the germline. We found that Y397F embryos exhibited reduced mesodermal fibronectin (FN) and osteopontin expression and died during mesoderm development akin to FAK kinase-dead mice. We identified myosin-1E (MYO1E), an actin-dependent molecular motor, to interact directly with the FAK FERM-kinase linker and induce FAK kinase activity and Y397 phosphorylation. Active FAK in turn accumulated in the nucleus where it led to the expression of osteopontin and other FN-type matrix in both mouse embryonic fibroblasts and human melanoma. Our data support a model in which FAK Y397 autophosphorylation is required for FAK function in vivo and is positively regulated by MYO1E.

U2 - 10.1073/pnas.1614894114

DO - 10.1073/pnas.1614894114

M3 - Journal article

C2 - 28348210

SN - 0027-8424

VL - 114

SP - 3933

EP - 3938

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 - 15

ER -

Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix

Abstract

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater