Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation

Haihua Gu; Joanne C. Pratt; Steven J. Burakoff; Benjamin G. Neel

doi:10.1016/S1097-2765(00)80288-9

Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation

Haihua Gu
, Joanne C. Pratt
, Steven J. Burakoff
, Benjamin G. Neel

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

288 Scopus citations

Abstract

Several components in cytokine signaling remain unidentified. We report the cloning and initial characterization of one such component, p97, a widely expressed scaffolding protein distantly related to Drosophila DOS and mammalian Gab1. Upon cytokine, growth factor, or antigen receptor stimulation, p97 becomes tyrosyl phosphorylated and associates with several SH2 domain-containing proteins, including SHP2. Expression of p97 mutants unable to bind SHP2 blocks cytokine-induced c-fos promoter activation, inhibiting Elk1-mediated and STAT5-mediated transactivation. Surprisingly, such mutants do not inhibit MAPK activation. Our results identify p97 as an important regulator of receptor signaling that controls a novel pathway to immediate-early gene activation and suggest multiple functions for SHP2 in cytokine receptor signaling.

Original language	English
Pages (from-to)	729-740
Number of pages	12
Journal	Molecular Cell
Volume	2
Issue number	6
DOIs	https://doi.org/10.1016/S1097-2765(00)80288-9
State	Published - Dec 1998
Externally published	Yes

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10.1016/S1097-2765(00)80288-9

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@article{94e1e5dd09f04ca68d235626b064f259,

title = "Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation",

abstract = "Several components in cytokine signaling remain unidentified. We report the cloning and initial characterization of one such component, p97, a widely expressed scaffolding protein distantly related to Drosophila DOS and mammalian Gab1. Upon cytokine, growth factor, or antigen receptor stimulation, p97 becomes tyrosyl phosphorylated and associates with several SH2 domain-containing proteins, including SHP2. Expression of p97 mutants unable to bind SHP2 blocks cytokine-induced c-fos promoter activation, inhibiting Elk1-mediated and STAT5-mediated transactivation. Surprisingly, such mutants do not inhibit MAPK activation. Our results identify p97 as an important regulator of receptor signaling that controls a novel pathway to immediate-early gene activation and suggest multiple functions for SHP2 in cytokine receptor signaling.",

author = "Haihua Gu and Pratt, \{Joanne C.\} and Burakoff, \{Steven J.\} and Neel, \{Benjamin G.\}",

note = "Funding Information: We thank R. Robsin, J. Neveu, D. Kirby, K. Pierce, D. Arnelle, E. Spooner, and W. S. Lane of the Harvard Microchemistry Facility for HPLC, mass spectrometry and peptide sequencing. We thank S. Kamatkar and D. Liu for excellent technical assistance, Drs. C. Carpenter and J. Timms (BIDMC) for many helpful suggestions and discussion during the course of this work, and Drs. L. C. Cantley, C. Carpenter, S. M. Thomas, and A.M. O{\textquoteright}Reilly (BIDMC), M. Greenberg (Children{\textquoteright}s Hospital, Boston, MA), and John Blenis (HMS) for critical reading of the manuscript. This work was supported by NIH grants R01-DK50693, PO1-DK50654 (to B. G. N.) and CA70758 (to S. J. B.). H. G. is supported by NRSA CA72144 from the NIH and J. C. P. was supported by The Medical Foundation, Inc. ",

year = "1998",

month = dec,

doi = "10.1016/S1097-2765(00)80288-9",

language = "English",

volume = "2",

pages = "729--740",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

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T1 - Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation

AU - Gu, Haihua

AU - Pratt, Joanne C.

AU - Burakoff, Steven J.

AU - Neel, Benjamin G.

N1 - Funding Information: We thank R. Robsin, J. Neveu, D. Kirby, K. Pierce, D. Arnelle, E. Spooner, and W. S. Lane of the Harvard Microchemistry Facility for HPLC, mass spectrometry and peptide sequencing. We thank S. Kamatkar and D. Liu for excellent technical assistance, Drs. C. Carpenter and J. Timms (BIDMC) for many helpful suggestions and discussion during the course of this work, and Drs. L. C. Cantley, C. Carpenter, S. M. Thomas, and A.M. O’Reilly (BIDMC), M. Greenberg (Children’s Hospital, Boston, MA), and John Blenis (HMS) for critical reading of the manuscript. This work was supported by NIH grants R01-DK50693, PO1-DK50654 (to B. G. N.) and CA70758 (to S. J. B.). H. G. is supported by NRSA CA72144 from the NIH and J. C. P. was supported by The Medical Foundation, Inc.

PY - 1998/12

Y1 - 1998/12

N2 - Several components in cytokine signaling remain unidentified. We report the cloning and initial characterization of one such component, p97, a widely expressed scaffolding protein distantly related to Drosophila DOS and mammalian Gab1. Upon cytokine, growth factor, or antigen receptor stimulation, p97 becomes tyrosyl phosphorylated and associates with several SH2 domain-containing proteins, including SHP2. Expression of p97 mutants unable to bind SHP2 blocks cytokine-induced c-fos promoter activation, inhibiting Elk1-mediated and STAT5-mediated transactivation. Surprisingly, such mutants do not inhibit MAPK activation. Our results identify p97 as an important regulator of receptor signaling that controls a novel pathway to immediate-early gene activation and suggest multiple functions for SHP2 in cytokine receptor signaling.

AB - Several components in cytokine signaling remain unidentified. We report the cloning and initial characterization of one such component, p97, a widely expressed scaffolding protein distantly related to Drosophila DOS and mammalian Gab1. Upon cytokine, growth factor, or antigen receptor stimulation, p97 becomes tyrosyl phosphorylated and associates with several SH2 domain-containing proteins, including SHP2. Expression of p97 mutants unable to bind SHP2 blocks cytokine-induced c-fos promoter activation, inhibiting Elk1-mediated and STAT5-mediated transactivation. Surprisingly, such mutants do not inhibit MAPK activation. Our results identify p97 as an important regulator of receptor signaling that controls a novel pathway to immediate-early gene activation and suggest multiple functions for SHP2 in cytokine receptor signaling.

UR - https://www.scopus.com/pages/publications/0032238298

U2 - 10.1016/S1097-2765(00)80288-9

DO - 10.1016/S1097-2765(00)80288-9

M3 - Article

C2 - 9885561

AN - SCOPUS:0032238298

SN - 1097-2765

VL - 2

SP - 729

EP - 740

JO - Molecular Cell

JF - Molecular Cell

IS - 6

ER -

Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation

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