Organization of functional domains in the docking protein p130Cas

Fariborz Nasertorabi; Miguel Garcia-Guzman; Klára Briknarová; Elise Larsen; Marnie L. Havert; Kristiina Vuori; Kathryn R. Ely

doi:10.1016/j.bbrc.2004.09.148

Organization of functional domains in the docking protein p130Cas

Fariborz Nasertorabi
, Miguel Garcia-Guzman
, Klára Briknarová
, Elise Larsen
, Marnie L. Havert
, Kristiina Vuori
, Kathryn R. Ely

Chemistry and Biochemistry

Sanford Burnham Prebys Medical Discovery Institute

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

12 Scopus citations

Abstract

The docking protein p130Cas becomes phosphorylated upon cell adhesion to extracellular matrix proteins, and is thought to play an essential role in cell transformation. Cas transmits signals through interactions with the Src-homology 3 (SH3) and Src-homology 2 domains of FAK or v-Crk signaling molecules, or with 14-3-3 protein, as well as phosphatases PTP1B and PTP-PEST. The large (130 kDa), multi-domain Cas molecule contains an SH3 domain, a Src-binding domain, a serine-rich protein interaction region, and a C-terminal region that participates in protein interactions implicated in antiestrogen resistance in breast cancer. In this study, as part of a long-term goal to examine the protein interactions of Cas by X-ray crystallography and nuclear magnetic resonance spectroscopy, molecular constructs were designed to express two adjacent domains, the serine-rich domain and the Src-binding domain, that each participate in intermolecular contacts dependent on protein phosphorylation. The protein products are soluble, homogeneous, monodisperse, and highly suitable for structural studies to define the role of Cas in integrin-mediated cell signaling.

Original language	English
Pages (from-to)	993-998
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	324
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2004.09.148
State	Published - Nov 19 2004

Funding

This work was supported by Grant #CA071560 from the National Cancer Institute, Grant #00-00512V-10030 from the California Research Program, Grant #8IB-0187 from the California Breast Cancer Research Program, and pre-doctoral fellowship #DAMD17-01-1-0169 (to F.N.) from the US Army Breast Cancer Research Program, and an award from the Swedish-American foundation. The authors are grateful to Lisa O’Brien for preparing the manuscript for publication.

Funder number
17-01-1-0169, 8IB-0187, 00-00512V-10030, R01CA071560

Keywords

14-3-3 protein
Cas family proteins
Integrin signaling
Protein design
Protein phosphorylation
Src family kinases

UN SDGs

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

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10.1016/j.bbrc.2004.09.148

Cite this

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title = "Organization of functional domains in the docking protein p130Cas",

abstract = "The docking protein p130Cas becomes phosphorylated upon cell adhesion to extracellular matrix proteins, and is thought to play an essential role in cell transformation. Cas transmits signals through interactions with the Src-homology 3 (SH3) and Src-homology 2 domains of FAK or v-Crk signaling molecules, or with 14-3-3 protein, as well as phosphatases PTP1B and PTP-PEST. The large (130 kDa), multi-domain Cas molecule contains an SH3 domain, a Src-binding domain, a serine-rich protein interaction region, and a C-terminal region that participates in protein interactions implicated in antiestrogen resistance in breast cancer. In this study, as part of a long-term goal to examine the protein interactions of Cas by X-ray crystallography and nuclear magnetic resonance spectroscopy, molecular constructs were designed to express two adjacent domains, the serine-rich domain and the Src-binding domain, that each participate in intermolecular contacts dependent on protein phosphorylation. The protein products are soluble, homogeneous, monodisperse, and highly suitable for structural studies to define the role of Cas in integrin-mediated cell signaling.",

keywords = "14-3-3 protein, Cas family proteins, Integrin signaling, Protein design, Protein phosphorylation, Src family kinases",

author = "Fariborz Nasertorabi and Miguel Garcia-Guzman and Kl{\'a}ra Briknarov{\'a} and Elise Larsen and Havert, \{Marnie L.\} and Kristiina Vuori and Ely, \{Kathryn R.\}",

note = "Funding Information: This work was supported by Grant \#CA071560 from the National Cancer Institute, Grant \#00-00512V-10030 from the California Research Program, Grant \#8IB-0187 from the California Breast Cancer Research Program, and pre-doctoral fellowship \#DAMD17-01-1-0169 (to F.N.) from the US Army Breast Cancer Research Program, and an award from the Swedish-American foundation. The authors are grateful to Lisa O{\textquoteright}Brien for preparing the manuscript for publication.",

year = "2004",

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doi = "10.1016/j.bbrc.2004.09.148",

language = "English",

volume = "324",

pages = "993--998",

journal = "Biochemical and Biophysical Research Communications",

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AU - Nasertorabi, Fariborz

AU - Garcia-Guzman, Miguel

AU - Briknarová, Klára

AU - Larsen, Elise

AU - Havert, Marnie L.

AU - Vuori, Kristiina

AU - Ely, Kathryn R.

N1 - Funding Information: This work was supported by Grant #CA071560 from the National Cancer Institute, Grant #00-00512V-10030 from the California Research Program, Grant #8IB-0187 from the California Breast Cancer Research Program, and pre-doctoral fellowship #DAMD17-01-1-0169 (to F.N.) from the US Army Breast Cancer Research Program, and an award from the Swedish-American foundation. The authors are grateful to Lisa O’Brien for preparing the manuscript for publication.

PY - 2004/11/19

Y1 - 2004/11/19

N2 - The docking protein p130Cas becomes phosphorylated upon cell adhesion to extracellular matrix proteins, and is thought to play an essential role in cell transformation. Cas transmits signals through interactions with the Src-homology 3 (SH3) and Src-homology 2 domains of FAK or v-Crk signaling molecules, or with 14-3-3 protein, as well as phosphatases PTP1B and PTP-PEST. The large (130 kDa), multi-domain Cas molecule contains an SH3 domain, a Src-binding domain, a serine-rich protein interaction region, and a C-terminal region that participates in protein interactions implicated in antiestrogen resistance in breast cancer. In this study, as part of a long-term goal to examine the protein interactions of Cas by X-ray crystallography and nuclear magnetic resonance spectroscopy, molecular constructs were designed to express two adjacent domains, the serine-rich domain and the Src-binding domain, that each participate in intermolecular contacts dependent on protein phosphorylation. The protein products are soluble, homogeneous, monodisperse, and highly suitable for structural studies to define the role of Cas in integrin-mediated cell signaling.

AB - The docking protein p130Cas becomes phosphorylated upon cell adhesion to extracellular matrix proteins, and is thought to play an essential role in cell transformation. Cas transmits signals through interactions with the Src-homology 3 (SH3) and Src-homology 2 domains of FAK or v-Crk signaling molecules, or with 14-3-3 protein, as well as phosphatases PTP1B and PTP-PEST. The large (130 kDa), multi-domain Cas molecule contains an SH3 domain, a Src-binding domain, a serine-rich protein interaction region, and a C-terminal region that participates in protein interactions implicated in antiestrogen resistance in breast cancer. In this study, as part of a long-term goal to examine the protein interactions of Cas by X-ray crystallography and nuclear magnetic resonance spectroscopy, molecular constructs were designed to express two adjacent domains, the serine-rich domain and the Src-binding domain, that each participate in intermolecular contacts dependent on protein phosphorylation. The protein products are soluble, homogeneous, monodisperse, and highly suitable for structural studies to define the role of Cas in integrin-mediated cell signaling.

KW - 14-3-3 protein

KW - Cas family proteins

KW - Integrin signaling

KW - Protein design

KW - Protein phosphorylation

KW - Src family kinases

UR - https://www.scopus.com/pages/publications/5444269960

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SN - 0006-291X

VL - 324

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EP - 998

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

Organization of functional domains in the docking protein p130Cas

Abstract

Funding

Keywords

UN SDGs

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