Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix
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Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix. / Heim, Joel B; Squirewell, Edwin J; Neu, Ancilla; Zocher, Georg; Sominidi-Damodaran, Sindhuja; Wyles, Saranya P; Nikolova, Ekaterina; Behrendt, Nille; Saunte, Ditte M; Lock-Andersen, Jorgen; Gaonkar, Krutika S; Yan, Huihuang; Sarkaria, Jann N; Krendel, Mira; van Deursen, Jan; Sprangers, Remco; Stehle, Thilo; Böttcher, Ralph T; Lee, Jeong-Heon; Ordog, Tamas; Meves, Alexander.
I: Proceedings of the National Academy of Sciences of the United States of America, Bind 114, Nr. 15, 2017, s. 3933-3938.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
Y1 - 2017
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
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
SN - 0027-8424
IS - 15
ER -
ID: 195545923