Phosphatidylinositol 3-kinase: Structure and expression of the 110 kd catalytic subunit

Ian D. Hiles; Masayuki Otsu; Stefano Volinia; Michael J. Fry; Ivan Gout; Ritu Dhand; George Panayotou; Fernanda Ruiz-Larrea; Andrew Thompson; Nicholas F. Totty; J. Justin Hsuan; Sara A. Courtneidge; Peter J. Parker; Michael D. Waterfield

doi:10.1016/0092-8674(92)90166-A

Phosphatidylinositol 3-kinase: Structure and expression of the 110 kd catalytic subunit

Ian D. Hiles
, Masayuki Otsu
, Stefano Volinia
, Michael J. Fry
, Ivan Gout
, Ritu Dhand
, George Panayotou
, Fernanda Ruiz-Larrea
, Andrew Thompson
, Nicholas F. Totty
, J. Justin Hsuan
, Sara A. Courtneidge
, Peter J. Parker
, Michael D. Waterfield

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

622 Scopus citations

Abstract

Purified bovine brain phosphatidylinositol 3-kinase (PI3-kinase) is composed of 85 kd and 110 kd subunits. The 85 kd subunit (p85α) lacks PI3-kinase activity and acts as an adaptor, coupling the 110 kd subunit (p110) to activated protein tyrosine kinases. Here the characterization of the p110 subunit is presented. cDNA cloning reveals p110 to be a 1068 aa protein related to Vps34p, a S. cerevisiae protein involved in the sorting of proteins to the vacuole. p110 expressed in insect cells possesses PI3-kinase activity and associates with p85α into an active p85α-p110 complex that binds the activated colony-stimulating factor 1 receptor. p110 expressed in COS-1 cells is catalytically active only when complexed with p85α.

Original language	English (US)
Pages (from-to)	419-429
Number of pages	11
Journal	Cell
Volume	70
Issue number	3
DOIs	https://doi.org/10.1016/0092-8674(92)90166-A
State	Published - Aug 7 1992
Externally published	Yes

Funding

We would like to thank the following people for help and materials provided during the course of this work: Dr. G. St. Whitley and Dr. A. Johnstone (St. Georges Hospital, London) for the SGBAF-1 cell line, Dr. M. Page (Wellcome Biotech, Beckenham, Kent) for the p36C baculovirus transfer vector, M. Jones (EMBL, Heidelberg) for help in the preparation of the ~110 C-terminal peptide antiserum, and Dr. C. Sherr (Howard Hughes Medical Institute, University of Tennessee, Memphis, Tennessee) for the CSF-1 receptor antiserum and cDNA. Finally, we would like to thank Mr. G. Scrace for help with DNA and protein sequence analysis, Mr. A. Sterling for oligonucleotide synthesis, and Dr. S. Emr for helpful discussions. I. G. was supported by a grant from Imperial Chemical Industries during part of his work on this project.

Funders
Imperial Chemical Industries

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/0092-8674(92)90166-A

Cite this

@article{67cdaf6578b5480b9648d4b55dcd9853,

title = "Phosphatidylinositol 3-kinase: Structure and expression of the 110 kd catalytic subunit",

abstract = "Purified bovine brain phosphatidylinositol 3-kinase (PI3-kinase) is composed of 85 kd and 110 kd subunits. The 85 kd subunit (p85α) lacks PI3-kinase activity and acts as an adaptor, coupling the 110 kd subunit (p110) to activated protein tyrosine kinases. Here the characterization of the p110 subunit is presented. cDNA cloning reveals p110 to be a 1068 aa protein related to Vps34p, a S. cerevisiae protein involved in the sorting of proteins to the vacuole. p110 expressed in insect cells possesses PI3-kinase activity and associates with p85α into an active p85α-p110 complex that binds the activated colony-stimulating factor 1 receptor. p110 expressed in COS-1 cells is catalytically active only when complexed with p85α.",

author = "Hiles, \{Ian D.\} and Masayuki Otsu and Stefano Volinia and Fry, \{Michael J.\} and Ivan Gout and Ritu Dhand and George Panayotou and Fernanda Ruiz-Larrea and Andrew Thompson and Totty, \{Nicholas F.\} and Hsuan, \{J. Justin\} and Courtneidge, \{Sara A.\} and Parker, \{Peter J.\} and Waterfield, \{Michael D.\}",

note = "Funding Information: We would like to thank the following people for help and materials provided during the course of this work: Dr. G. St. Whitley and Dr. A. Johnstone (St. Georges Hospital, London) for the SGBAF-1 cell line, Dr. M. Page (Wellcome Biotech, Beckenham, Kent) for the p36C baculovirus transfer vector, M. Jones (EMBL, Heidelberg) for help in the preparation of the \textasciitilde{}110 C-terminal peptide antiserum, and Dr. C. Sherr (Howard Hughes Medical Institute, University of Tennessee, Memphis, Tennessee) for the CSF-1 receptor antiserum and cDNA. Finally, we would like to thank Mr. G. Scrace for help with DNA and protein sequence analysis, Mr. A. Sterling for oligonucleotide synthesis, and Dr. S. Emr for helpful discussions. I. G. was supported by a grant from Imperial Chemical Industries during part of his work on this project.",

year = "1992",

month = aug,

day = "7",

doi = "10.1016/0092-8674(92)90166-A",

language = "English (US)",

volume = "70",

pages = "419--429",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "3",

}

TY - JOUR

T1 - Phosphatidylinositol 3-kinase

T2 - Structure and expression of the 110 kd catalytic subunit

AU - Hiles, Ian D.

AU - Otsu, Masayuki

AU - Volinia, Stefano

AU - Fry, Michael J.

AU - Gout, Ivan

AU - Dhand, Ritu

AU - Panayotou, George

AU - Ruiz-Larrea, Fernanda

AU - Thompson, Andrew

AU - Totty, Nicholas F.

AU - Hsuan, J. Justin

AU - Courtneidge, Sara A.

AU - Parker, Peter J.

AU - Waterfield, Michael D.

N1 - Funding Information: We would like to thank the following people for help and materials provided during the course of this work: Dr. G. St. Whitley and Dr. A. Johnstone (St. Georges Hospital, London) for the SGBAF-1 cell line, Dr. M. Page (Wellcome Biotech, Beckenham, Kent) for the p36C baculovirus transfer vector, M. Jones (EMBL, Heidelberg) for help in the preparation of the ~110 C-terminal peptide antiserum, and Dr. C. Sherr (Howard Hughes Medical Institute, University of Tennessee, Memphis, Tennessee) for the CSF-1 receptor antiserum and cDNA. Finally, we would like to thank Mr. G. Scrace for help with DNA and protein sequence analysis, Mr. A. Sterling for oligonucleotide synthesis, and Dr. S. Emr for helpful discussions. I. G. was supported by a grant from Imperial Chemical Industries during part of his work on this project.

PY - 1992/8/7

Y1 - 1992/8/7

N2 - Purified bovine brain phosphatidylinositol 3-kinase (PI3-kinase) is composed of 85 kd and 110 kd subunits. The 85 kd subunit (p85α) lacks PI3-kinase activity and acts as an adaptor, coupling the 110 kd subunit (p110) to activated protein tyrosine kinases. Here the characterization of the p110 subunit is presented. cDNA cloning reveals p110 to be a 1068 aa protein related to Vps34p, a S. cerevisiae protein involved in the sorting of proteins to the vacuole. p110 expressed in insect cells possesses PI3-kinase activity and associates with p85α into an active p85α-p110 complex that binds the activated colony-stimulating factor 1 receptor. p110 expressed in COS-1 cells is catalytically active only when complexed with p85α.

AB - Purified bovine brain phosphatidylinositol 3-kinase (PI3-kinase) is composed of 85 kd and 110 kd subunits. The 85 kd subunit (p85α) lacks PI3-kinase activity and acts as an adaptor, coupling the 110 kd subunit (p110) to activated protein tyrosine kinases. Here the characterization of the p110 subunit is presented. cDNA cloning reveals p110 to be a 1068 aa protein related to Vps34p, a S. cerevisiae protein involved in the sorting of proteins to the vacuole. p110 expressed in insect cells possesses PI3-kinase activity and associates with p85α into an active p85α-p110 complex that binds the activated colony-stimulating factor 1 receptor. p110 expressed in COS-1 cells is catalytically active only when complexed with p85α.

UR - https://www.scopus.com/pages/publications/0026720350

UR - https://www.scopus.com/pages/publications/0026720350#tab=citedBy

U2 - 10.1016/0092-8674(92)90166-A

DO - 10.1016/0092-8674(92)90166-A

M3 - Article

C2 - 1322797

AN - SCOPUS:0026720350

SN - 0092-8674

VL - 70

SP - 419

EP - 429

JO - Cell

JF - Cell

IS - 3

ER -

Phosphatidylinositol 3-kinase: Structure and expression of the 110 kd catalytic subunit

Abstract

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ASJC Scopus subject areas

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