Activated Galpha subunits can inhibit multiple signal transduction pathways during Dictyostelium development.

Abstract:

:Mutations impairing the GTPase activity of G protein Galpha subunits can result in activated Galpha subunits that affect signal transduction and cellular responses and, in some cases, promote tumor formation. An analogous mutation in the Dictyostelium Galpha4 subunit gene (Q200L substitution) was constructed and found to inhibit Galpha4-mediated responses to folic acid, including the accumulation of cyclic nucleotides and chemotactic cell movement. The Galpha4-Q200L subunit also severely inhibited responses to cAMP, including cyclic nucleotide accumulation, cAMP chemotaxis, and cellular aggregation. An analogous mutation in the Galpha2 subunit (Q208L substitution), previously reported to inhibit cAMP responses (K. Okaichi et al., 1992, Mol. Biol. Cell 3, 735-747), was also found to partially inhibit folic acid chemotaxis. Chemotactic responses to folic acid and cAMP and developmental aggregation were also inhibited by a mutant Galpha5 subunit with the analogous alteration (Q199L substitution). All aggregation-defective Galpha mutants were capable of multicellular development after a temporary incubation at 4 degrees C and this development was found to be dependent on wild-type Galpha4 function. This study indicates that mutant Galpha subunits can inhibit signal transduction pathways mediated by other Galpha subunits.

journal_name

Dev Biol

journal_title

Developmental biology

authors

Srinivasan J,Gundersen RE,Hadwiger JA

doi

10.1006/dbio.1999.9474

subject

Has Abstract

pub_date

1999-11-15 00:00:00

pages

443-52

issue

2

eissn

0012-1606

issn

1095-564X

pii

S0012-1606(99)99474-5

journal_volume

215

pub_type

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