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(Received for publication, November 4, 1996, and in revised form, December 17, 1996)
From the Terry Fox Laboratory, British Columbia Cancer Agency, and
The Biomedical Research Centre, University of British Columbia,
Vancouver, British Columbia V5Z 1L3, Canada
In this study we have investigated the role that
the Src homology 2 domain (SH2) of the 145-kDa 5-phosphatase,
SH2-containing inositol phosphatase (SHIP), plays in three of the
properties that have been associated with this protein following
cytokine stimulation: its association with Shc, its tyrosine
phosphorylation, and its inhibition of hemopoietic cell growth.
In vitro studies using this SH2 domain revealed that it was
capable of binding directly to the Tyr(P)317 motif of Shc
with a KD of approximately 290 nM, in
keeping with other specific SH2/Tyr(P) interactions. In
vivo analysis revealed the SH2 and NPXpY motifs of
SHIP acted together, with the Tyr(P)317 and phosphotyrosine
binding (PTB) domains of Shc, respectively, to ensure a high affinity
SHIP·Shc complex. Expression of cDNAs encoding
hemagglutinin-tagged wild type and SH2-inactivated forms of SHIP in the
murine hemopoietic cell line DA-ER revealed that wild type SHIP becomes
both tyrosine-phosphorylated and associated with Shc following
interleukin-3 stimulation, as expected, but the SH2-inactivated SHIPs
do neither. Moreover, while the growth rates of parental DA-ER cells
and cells expressing these various SHIP constructs are identical, the
wild type SHIP-expressing cells die, via programmed cell death, far
more rapidly than parental cells. Cells expressing SH2-inactivated
SHIPs, on the other hand, show either a reduced or no effect on
apoptosis. These results suggest that the SH2 domain of SHIP is
required not only for the tyrosine phosphorylation of SHIP and Shc
association following cytokine stimulation but also for its induction
of apoptosis.
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N. Gupta, A. M. Scharenberg, D. A. Fruman, L. C. Cantley, J.-P. Kinet, and E. O. Long The SH2 Domain-containing Inositol 5'-Phosphatase (SHIP) Recruits the p85 Subunit of Phosphoinositide 3-Kinase during Fcgamma RIIb1-mediated Inhibition of B Cell Receptor Signaling J. Biol. Chem., March 12, 1999; 274(11): 7489 - 7494. [Abstract] [Full Text] [PDF]
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F. Walker, A. Kato, L. J. Gonez, M. L. Hibbs, N. Pouliot, A. Levitzki, and A. W. Burgess Activation of the Ras/Mitogen-Activated Protein Kinase Pathway by Kinase-Defective Epidermal Growth Factor Receptors Results in Cell Survival but Not Proliferation Mol. Cell. Biol., December 1, 1998; 18(12): 7192 - 7204. [Abstract] [Full Text]
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Q. Liu, A. J. Oliveira-Dos-Santos, S. Mariathasan, D. Bouchard, J. Jones, R. Sarao, I. Kozieradzki, P. S. Ohashi, J. M. Penninger, and D. J. Dumont The Inositol Polyphosphate 5-Phosphatase Ship Is a Crucial Negative Regulator of B Cell Antigen Receptor Signaling J. Exp. Med., October 5, 1998; 188(7): 1333 - 1342. [Abstract] [Full Text] [PDF]
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E. W. Murray and S. M. Robbins Antibody Cross-linking of the Glycosylphosphatidylinositol-linked Protein CD59 on Hematopoietic Cells Induces Signaling Pathways Resembling Activation by Complement J. Biol. Chem., September 25, 1998; 273(39): 25279 - 25284. [Abstract] [Full Text] [PDF]
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J. E. Damen, L. Liu, M. D. Ware, M. Ermolaeva, P. W. Majerus, and G. Krystal Multiple Forms of the SH2-Containing Inositol Phosphatase, SHIP, Are Generated by C-Terminal Truncation Blood, August 15, 1998; 92(4): 1199 - 1205. [Abstract] [Full Text] [PDF]
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T. Habib, J. A. Hejna, R. E. Moses, and S. J. Decker Growth Factors and Insulin Stimulate Tyrosine Phosphorylation of the 51C/SHIP2 Protein J. Biol. Chem., July 17, 1998; 273(29): 18605 - 18609. [Abstract] [Full Text] [PDF]
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C. D. Helgason, J. E. Damen, P. Rosten, R. Grewal, P. Sorensen, S. M. Chappel, A. Borowski, F. Jirik, G. Krystal, and R. K. Humphries Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span Genes & Dev., June 1, 1998; 12(11): 1610 - 1620. [Abstract] [Full Text]
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M. G. Hunter and B. R. Avalos Phosphatidylinositol 3'-Kinase and SH2-Containing Inositol Phosphatase (SHIP) Are Recruited by Distinct Positive and Negative Growth-Regulatory Domains in the Granulocyte Colony-Stimulating Factor Receptor J. Immunol., May 15, 1998; 160(10): 4979 - 4987. [Abstract] [Full Text] [PDF]
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A. P. Kennedy, A. Sekulic, B. J. Irvin, A. E. Nilson, S. M. Dilworth, and R. T. Abraham Polyomavirus Middle T Antigen as a Probe for T Cell Antigen Receptor-coupled Signaling Pathways J. Biol. Chem., May 8, 1998; 273(19): 11505 - 11513. [Abstract] [Full Text] [PDF]
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Q. Liu, F. Shalaby, J. Jones, D. Bouchard, and D. J. Dumont The SH2-Containing Inositol Polyphosphate 5-Phosphatase, Ship, Is Expressed During Hematopoiesis and Spermatogenesis Blood, April 15, 1998; 91(8): 2753 - 2759. [Abstract] [Full Text] [PDF]
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O. Malbec, D. C. Fong, M. Turner, V. L. J. Tybulewicz, J. C. Cambier, W. H. Fridman, and M. Daeron Fc{epsilon} Receptor I-Associated lyn-Dependent Phosphorylation of Fc{gamma} Receptor IIB During Negative Regulation of Mast Cell Activation J. Immunol., February 15, 1998; 160(4): 1647 - 1658. [Abstract] [Full Text] [PDF]
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 Z. Songyang, D. Baltimore, L. C. Cantley, D. R. Kaplan, and T. F. Franke Interleukin 3-dependent survival by the Akt protein kinase PNAS, October 14, 1997; 94(21): 11345 - 11350. [Abstract] [Full Text] [PDF]
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L. Liu, J. E. Damen, M. D. Ware, and G. Krystal Interleukin-3 Induces the Association of the Inositol 5-Phosphatase SHIP with SHP2 J. Biol. Chem., April 25, 1997; 272(17): 10998 - 11001. [Abstract] [Full Text] [PDF]
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C. Giallourakis, M. Kashiwada, P.-Y. Pan, N. Danial, H. Jiang, J. Cambier, K. M. Coggeshall, and P. Rothman Positive Regulation of Interleukin-4-mediated Proliferation by the SH2-containing Inositol-5'-phosphatase J. Biol. Chem., September 15, 2000; 275(38): 29275 - 29282. [Abstract] [Full Text] [PDF]
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M. Sattler, S. Verma, Y. B. Pride, R. Salgia, L. R. Rohrschneider, and J. D. Griffin SHIP1, an SH2 Domain Containing Polyinositol-5-phosphatase, Regulates Migration through Two Critical Tyrosine Residues and Forms a Novel Signaling Complex with DOK1 and CRKL J. Biol. Chem., January 19, 2001; 276(4): 2451 - 2458. [Abstract] [Full Text] [PDF]
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X. Pesesse, V. Dewaste, F. De Smedt, M. Laffargue, S. Giuriato, C. Moreau, B. Payrastre, and C. Erneux The Src Homology 2 Domain Containing Inositol 5-Phosphatase SHIP2 Is Recruited to the Epidermal Growth Factor (EGF) Receptor and Dephosphorylates Phosphatidylinositol 3,4,5-Trisphosphate in EGF-stimulated COS-7 Cells J. Biol. Chem., July 20, 2001; 276(30): 28348 - 28355. [Abstract] [Full Text] [PDF]
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