Mutant alpha-subunit of the G protein G12 activates proliferation and inhibits differentiation of 3T3-F442A preadipocytes.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

We studied the G protein alpha-subunit Galpha12 in various tissues and cell lines. Significant amounts of Galpha12 were detected by immunoblots in liver, chromaffin cells, RINm5F cells, 3T3-F442A cells, and preadipocytes, but not in adipocytes, sperm, kidney, NB2A cells, or brain. To study the role of Galpha12 in adipose tissue differentiation, the preadipocyte cell line 3T3-F442A was transfected with wild-type Galpha12 or a constitutively activated mutant of Galpha12. Stable expression of the activated mutant of Galpha12 stimulated cell growth and inhibited preadipocyte differentiation. In contrast, wild-type Galpha12 overexpression inhibited preadipocyte differentiation, without any effect on cell proliferation. The role of Galpah12 on the Raf/MEK/mitogen-activating protein kinase (MAPK) cascade was studied. In confluent preadipocytes, expression of the activated mutant of Galpha12 induced an increase in B-Raf expression, but no change in MAPK activity. Differentiation was associated with a decrease in MAPK activity in control 3T3-F442A cells. Wild-type Galpha12 overexpression prevented the decrease in MAPK activity and induced MEK1, but not B-Raf, expression. Moreover, the activated mutant of Galpha12 induced an increase in MAPK activity and in the expression of both MEK1 and B-Raf. These data indicate that the activated mutant of Galpha12 stimulates the proliferation of 3T3

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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