Ras proteins increase Ca2+‐responsiveness of smooth muscle contraction

FEBS Letters

Pfitzer, G.¹  Satoh, S.¹  Rensland, H.² 

[1] II. Physiologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 326, D-6900 Heidelberg, Germany;Max Planck Institut für Medizinische Forschung, Jahnstr. 29, D-6900 Heidelberg, Germany

关键词: Ras p21;    Permeabilized microartery;    Ca2+-sensitivity;    Smooth muscle;    Tyrosine phosphorylation;    G protein;    Gpp(NH)p;    guanylyl-5'-imidodiphosphate;    GAP;    GTPase activating protein;    G protein;    GTP-binding protein;    c-ras p21;    wild type H-ras p21;    v-ras p21;    mutant H-ras p21 (p21[G12V]);    HEPES;    N-[2-hydroxyethyl]piperazine-N-[2-ethanesulfonic acid];   

DOI  :  10.1016/0014-5793(93)81395-G

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

G-proteins may be involved in receptor-mediated Ca²⁺-sensitization of smooth muscle contraction, but the responsible G-proteins are not yet known. Here we show that in β-escin skinned mesenteric microarteries, H-ras p21 proteins, preactivated with GTP or GTP γ S, increase force at constant submaximal Ca²⁺ (pCa 6.3) concentration dependently. The GTP-bound form of the wild-type H-ras p21 and the oncogenic mutant (p21[G12V]) were equally effective. The nucleotide-free and the inactive GDP-bound form of ras p21 had no effect on force. The tyrosine kinase inhibitor, tyrphostin, partially reversed the effect of the ras proteins in the GTP-bound form on force. Thus, ras proteins mimic the Ca²⁺-sensitizing effect of GTPγS and vasoconstrictors in mesenteric microarteries which may involve tyrosine phosphorylation.

【 授权许可】

Unknown