Calmodulin and PI3K Signaling in KRAS Cancers

Ruth Nussinov; Guanqiao Wang; Chung Jung Tsai; Hyunbum Jang; Shaoyong Lu; Avik Banerjee; Jian Zhang; Vadim Gaponenko

doi:10.1016/j.trecan.2017.01.007

Calmodulin and PI3K Signaling in KRAS Cancers

Ruth Nussinov^*, Guanqiao Wang, Chung Jung Tsai, Hyunbum Jang, Shaoyong Lu, Avik Banerjee, Jian Zhang, Vadim Gaponenko

^*Corresponding author for this work

Human Molecular Genetics Biochemistry

Research output: Contribution to journal › Review article › peer-review

Abstract

Calmodulin (CaM) uniquely promotes signaling by oncogenic K-Ras, but not by N-Ras or H-Ras. How CaM interacts with K-Ras and how this stimulates cell proliferation are among the most challenging questions in KRAS-driven cancers. Earlier data pointed to the formation of a ternary complex consisting of K-Ras, phosphatidylinositide-3-kinase α (PI3Kα), and CaM. Recent data indicate that phosphorylated CaM binds to the Src homology 2 (SH2) domains of the p85 subunit of PI3Kα and activates it. Modeling suggests that the high-affinity interaction between the phosphorylated CaM tyrosine motif and PI3Kα can promote full PI3Kα activation by oncogenic K-Ras. This review discusses the role of CaM in PI3K signaling at the membrane in KRAS-driven cancers. This is significant because it may help the development of K-Ras-specific pharmacology.

Original language	English
Pages (from-to)	214-224
Number of pages	11
Journal	Trends in Cancer
Volume	3
Issue number	3
DOIs	https://doi.org/10.1016/j.trecan.2017.01.007
State	Published - 1 Mar 2017

UN SDGs

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

Access to Document

10.1016/j.trecan.2017.01.007

Cite this

@article{91191a270ed34c418f6b93adc7da873f,

title = "Calmodulin and PI3K Signaling in KRAS Cancers",

abstract = "Calmodulin (CaM) uniquely promotes signaling by oncogenic K-Ras, but not by N-Ras or H-Ras. How CaM interacts with K-Ras and how this stimulates cell proliferation are among the most challenging questions in KRAS-driven cancers. Earlier data pointed to the formation of a ternary complex consisting of K-Ras, phosphatidylinositide-3-kinase α (PI3Kα), and CaM. Recent data indicate that phosphorylated CaM binds to the Src homology 2 (SH2) domains of the p85 subunit of PI3Kα and activates it. Modeling suggests that the high-affinity interaction between the phosphorylated CaM tyrosine motif and PI3Kα can promote full PI3Kα activation by oncogenic K-Ras. This review discusses the role of CaM in PI3K signaling at the membrane in KRAS-driven cancers. This is significant because it may help the development of K-Ras-specific pharmacology.",

author = "Ruth Nussinov and Guanqiao Wang and Tsai, {Chung Jung} and Hyunbum Jang and Shaoyong Lu and Avik Banerjee and Jian Zhang and Vadim Gaponenko",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = mar,

day = "1",

doi = "10.1016/j.trecan.2017.01.007",

language = "אנגלית",

volume = "3",

pages = "214--224",

journal = "Trends in Cancer",

issn = "2405-8033",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Calmodulin and PI3K Signaling in KRAS Cancers

AU - Nussinov, Ruth

AU - Wang, Guanqiao

AU - Tsai, Chung Jung

AU - Jang, Hyunbum

AU - Lu, Shaoyong

AU - Banerjee, Avik

AU - Zhang, Jian

AU - Gaponenko, Vadim

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Calmodulin (CaM) uniquely promotes signaling by oncogenic K-Ras, but not by N-Ras or H-Ras. How CaM interacts with K-Ras and how this stimulates cell proliferation are among the most challenging questions in KRAS-driven cancers. Earlier data pointed to the formation of a ternary complex consisting of K-Ras, phosphatidylinositide-3-kinase α (PI3Kα), and CaM. Recent data indicate that phosphorylated CaM binds to the Src homology 2 (SH2) domains of the p85 subunit of PI3Kα and activates it. Modeling suggests that the high-affinity interaction between the phosphorylated CaM tyrosine motif and PI3Kα can promote full PI3Kα activation by oncogenic K-Ras. This review discusses the role of CaM in PI3K signaling at the membrane in KRAS-driven cancers. This is significant because it may help the development of K-Ras-specific pharmacology.

AB - Calmodulin (CaM) uniquely promotes signaling by oncogenic K-Ras, but not by N-Ras or H-Ras. How CaM interacts with K-Ras and how this stimulates cell proliferation are among the most challenging questions in KRAS-driven cancers. Earlier data pointed to the formation of a ternary complex consisting of K-Ras, phosphatidylinositide-3-kinase α (PI3Kα), and CaM. Recent data indicate that phosphorylated CaM binds to the Src homology 2 (SH2) domains of the p85 subunit of PI3Kα and activates it. Modeling suggests that the high-affinity interaction between the phosphorylated CaM tyrosine motif and PI3Kα can promote full PI3Kα activation by oncogenic K-Ras. This review discusses the role of CaM in PI3K signaling at the membrane in KRAS-driven cancers. This is significant because it may help the development of K-Ras-specific pharmacology.

UR - http://www.scopus.com/inward/record.url?scp=85013073480&partnerID=8YFLogxK

U2 - 10.1016/j.trecan.2017.01.007

DO - 10.1016/j.trecan.2017.01.007

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.systematicreview???

AN - SCOPUS:85013073480

SN - 2405-8033

VL - 3

SP - 214

EP - 224

JO - Trends in Cancer

JF - Trends in Cancer

IS - 3

ER -

Calmodulin and PI3K Signaling in KRAS Cancers

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this