Involvement of the Protein Tyrosine Phosphatase SHP-1 in Ras-mediated Activation of the Mitogen-activated Protein Kinase Pathway

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1996 Nov 1

PMID 8887625

Citations 14

Authors

S Krautwald

D Buscher

V Kummer

S Buder

M Baccarini

Affiliations

Soon will be listed here.

Abstract

Ubiquitously expressed SH2-containing tyrosine phosphatases interact physically with tyrosine kinase receptors or their substrates and relay positive mitogenic signals via the activation of the Ras-mitogen-activated protein kinase (MAPK) pathway. Conversely, the structurally related phosphatase SHP-1 is predominantly expressed in hemopoietic cells and becomes tyrosine phosphorylated upon colony-stimulating factor 1 treatment of macrophages without associating with the colony-stimulating factor 1 receptor tyrosine kinase. Mice lacking functional SHP-1 (me/me and me(v)/me(v)) develop systemic autoimmune disease with accumulation of macrophages, suggesting that SHP-1 may be a negative regulator of hemopoietic cell growth. By using macrophages expressing dominant negative Ras and the me(v)/me(v) mouse mutant, we show that SHP-1 is activated in the course of mitogenic signal transduction in a Ras-dependent manner and that its activity is necessary for the Ras-dependent activation of the MAPK pathway but not of the Raf-1 kinase. Consistent with a role for SHP-1 as an intermediate between Ras and the MEK-MAPK pathway, Ras-independent activation of the latter kinases by bacterial lipopolysaccharide occurred normally in me(v)/me(v) cells. Our results sharply accentuate the diversity of signal transduction in mammalian cells, in which the same signaling intermediates can be rearranged to form different pathways.

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References

Xiao S, Rose D, Sasaoka T, Maegawa H, Burke Jr T, Roller P . Syp (SH-PTP2) is a positive mediator of growth factor-stimulated mitogenic signal transduction. J Biol Chem. 1994; 269(33):21244-8. View

Lioubin M, Myles G, Carlberg K, Bowtell D, Rohrschneider L . Shc, Grb2, Sos1, and a 150-kilodalton tyrosine-phosphorylated protein form complexes with Fms in hematopoietic cells. Mol Cell Biol. 1994; 14(9):5682-91. PMC: 359093. DOI: 10.1128/mcb.14.9.5682-5691.1994. View

Johnson G . Ras-dependent growth factor regulation of MEK kinase in PC12 cells. Science. 1994; 265(5177):1458-61. DOI: 10.1126/science.8073291. View

Bignon J, Siminovitch K . Identification of PTP1C mutation as the genetic defect in motheaten and viable motheaten mice: a step toward defining the roles of protein tyrosine phosphatases in the regulation of hemopoietic cell differentiation and function. Clin Immunol Immunopathol. 1994; 73(2):168-79. DOI: 10.1006/clin.1994.1185. View

Noguchi T, Matozaki T, Horita K, Fujioka Y, Kasuga M . Role of SH-PTP2, a protein-tyrosine phosphatase with Src homology 2 domains, in insulin-stimulated Ras activation. Mol Cell Biol. 1994; 14(10):6674-82. PMC: 359197. DOI: 10.1128/mcb.14.10.6674-6682.1994. View

Jaiswal R, Moodie S, Wolfman A, Landreth G . The mitogen-activated protein kinase cascade is activated by B-Raf in response to nerve growth factor through interaction with p21ras. Mol Cell Biol. 1994; 14(10):6944-53. PMC: 359225. DOI: 10.1128/mcb.14.10.6944-6953.1994. View

Kikuchi A, Demo S, Ye Z, Chen Y, Williams L . ralGDS family members interact with the effector loop of ras p21. Mol Cell Biol. 1994; 14(11):7483-91. PMC: 359284. DOI: 10.1128/mcb.14.11.7483-7491.1994. View

Hipskind R, Buscher D, Nordheim A, Baccarini M . Ras/MAP kinase-dependent and -independent signaling pathways target distinct ternary complex factors. Genes Dev. 1994; 8(15):1803-16. DOI: 10.1101/gad.8.15.1803. View

Catling A, Reuter C, Cox M, Parsons S, Weber M . Partial purification of a mitogen-activated protein kinase kinase activator from bovine brain. Identification as B-Raf or a B-Raf-associated activity. J Biol Chem. 1994; 269(47):30014-21. View

10.

Hofer F, Fields S, Schneider C, Martin G . Activated Ras interacts with the Ral guanine nucleotide dissociation stimulator. Proc Natl Acad Sci U S A. 1994; 91(23):11089-93. PMC: 45172. DOI: 10.1073/pnas.91.23.11089. View

11.

Buscher D, Hipskind R, Krautwald S, Reimann T, Baccarini M . Ras-dependent and -independent pathways target the mitogen-activated protein kinase network in macrophages. Mol Cell Biol. 1995; 15(1):466-75. PMC: 231993. DOI: 10.1128/MCB.15.1.466. View

12.

Spaargaren M, Bischoff J . Identification of the guanine nucleotide dissociation stimulator for Ral as a putative effector molecule of R-ras, H-ras, K-ras, and Rap. Proc Natl Acad Sci U S A. 1994; 91(26):12609-13. PMC: 45488. DOI: 10.1073/pnas.91.26.12609. View

13.

Jin D, Jameson S, Reddy M, Schenkman D, Ostrowski M . Alterations in differentiation and behavior of monocytic phagocytes in transgenic mice that express dominant suppressors of ras signaling. Mol Cell Biol. 1995; 15(2):693-703. PMC: 231933. DOI: 10.1128/MCB.15.2.693. View

14.

Yamauchi K, Milarski K, Saltiel A, Pessin J . Protein-tyrosine-phosphatase SHPTP2 is a required positive effector for insulin downstream signaling. Proc Natl Acad Sci U S A. 1995; 92(3):664-8. PMC: 42680. DOI: 10.1073/pnas.92.3.664. View

15.

Sun H, Tonks N . The coordinated action of protein tyrosine phosphatases and kinases in cell signaling. Trends Biochem Sci. 1994; 19(11):480-5. DOI: 10.1016/0968-0004(94)90134-1. View

16.

Tang T, Freeman Jr R, OReilly A, Neel B, Sokol S . The SH2-containing protein-tyrosine phosphatase SH-PTP2 is required upstream of MAP kinase for early Xenopus development. Cell. 1995; 80(3):473-83. DOI: 10.1016/0092-8674(95)90498-0. View

17.

Yatani A, Okabe K, Polakis P, Halenbeck R, McCormick F, Brown A . ras p21 and GAP inhibit coupling of muscarinic receptors to atrial K+ channels. Cell. 1990; 61(5):769-76. DOI: 10.1016/0092-8674(90)90187-j. View

18.

Cai H, Szeberenyi J, Cooper G . Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells. Mol Cell Biol. 1990; 10(10):5314-23. PMC: 361223. DOI: 10.1128/mcb.10.10.5314-5323.1990. View

19.

Baccarini M, Sabatini D, App H, Rapp U, Stanley E . Colony stimulating factor-1 (CSF-1) stimulates temperature dependent phosphorylation and activation of the RAF-1 proto-oncogene product. EMBO J. 1990; 9(11):3649-57. PMC: 552119. DOI: 10.1002/j.1460-2075.1990.tb07576.x. View

20.

Farnsworth C, Feig L . Dominant inhibitory mutations in the Mg(2+)-binding site of RasH prevent its activation by GTP. Mol Cell Biol. 1991; 11(10):4822-9. PMC: 361448. DOI: 10.1128/mcb.11.10.4822-4829.1991. View