Abstract
The phosphoinositide 3-kinase (PI3K) family includes eight distinct catalytic subunits and seven regulatory subunits. Only two PI3Ks are directly regulated downstream from G protein-coupled receptors (GPCRs): the class I enzymes PI3Kβ and PI3Kγ. Both enzymes produce phosphatidylinositol 3,4,5-trisposphate in vivo and are regulated by both heterotrimeric G proteins and small GTPases from the Ras or Rho families. However, PI3Kβ is also regulated by direct interactions with receptor tyrosine kinases (RTKs) and their tyrosine phosphorylated substrates, and similar to the class II and III PI3Ks, it binds activated Rab5. The unusually complex regulation of PI3Kβ by small and trimeric G proteins and RTKs leads to a rich landscape of signaling responses at the cellular and organismic levels. This review focuses first on the regulation of PI3Kβ activity in vitro and in cells, and then summarizes the biology of PI3Kβ signaling in distinct tissues and in human disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 536-555 |
| Number of pages | 20 |
| Journal | Endocrinology |
| Volume | 160 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2019 |
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ASJC Scopus subject areas
- Endocrinology
Cite this
PI3Kβ-A Versatile Transducer for GPCR, RTK, and Small GTPase Signaling. / Bresnick, Anne R.; Backer, Jonathan M.
In: Endocrinology, Vol. 160, No. 3, 01.03.2019, p. 536-555.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PI3Kβ-A Versatile Transducer for GPCR, RTK, and Small GTPase Signaling
AU - Bresnick, Anne R.
AU - Backer, Jonathan M.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - The phosphoinositide 3-kinase (PI3K) family includes eight distinct catalytic subunits and seven regulatory subunits. Only two PI3Ks are directly regulated downstream from G protein-coupled receptors (GPCRs): the class I enzymes PI3Kβ and PI3Kγ. Both enzymes produce phosphatidylinositol 3,4,5-trisposphate in vivo and are regulated by both heterotrimeric G proteins and small GTPases from the Ras or Rho families. However, PI3Kβ is also regulated by direct interactions with receptor tyrosine kinases (RTKs) and their tyrosine phosphorylated substrates, and similar to the class II and III PI3Ks, it binds activated Rab5. The unusually complex regulation of PI3Kβ by small and trimeric G proteins and RTKs leads to a rich landscape of signaling responses at the cellular and organismic levels. This review focuses first on the regulation of PI3Kβ activity in vitro and in cells, and then summarizes the biology of PI3Kβ signaling in distinct tissues and in human disease.
AB - The phosphoinositide 3-kinase (PI3K) family includes eight distinct catalytic subunits and seven regulatory subunits. Only two PI3Ks are directly regulated downstream from G protein-coupled receptors (GPCRs): the class I enzymes PI3Kβ and PI3Kγ. Both enzymes produce phosphatidylinositol 3,4,5-trisposphate in vivo and are regulated by both heterotrimeric G proteins and small GTPases from the Ras or Rho families. However, PI3Kβ is also regulated by direct interactions with receptor tyrosine kinases (RTKs) and their tyrosine phosphorylated substrates, and similar to the class II and III PI3Ks, it binds activated Rab5. The unusually complex regulation of PI3Kβ by small and trimeric G proteins and RTKs leads to a rich landscape of signaling responses at the cellular and organismic levels. This review focuses first on the regulation of PI3Kβ activity in vitro and in cells, and then summarizes the biology of PI3Kβ signaling in distinct tissues and in human disease.
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U2 - 10.1210/en.2018-00843
DO - 10.1210/en.2018-00843
M3 - Article
C2 - 30601996
AN - SCOPUS:85061585535
VL - 160
SP - 536
EP - 555
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 3
ER -