Homeodomain-interacting protein kinase regulates Yorkie activity to promote tissue growth

Joanna Chen1, Esther M Verheyen

  • 1Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.

Current Biology : CB
|July 31, 2012
PubMed

Insights

Homeodomain-interacting protein kinases (Hipks) promote Yorkie (Yki) activity, a key component of the Hippo pathway. This study identifies Hipk as the first kinase that positively regulates Yki, impacting tissue growth.

Area of Science:

  • Cell biology
  • Molecular biology
  • Developmental biology

Background:

  • The Hippo pathway (Hpo) is a crucial regulator of tissue size, controlling cell proliferation and apoptosis.
  • The core Hippo pathway kinase cascade inhibits the transcriptional effector Yorkie (Yki).
  • Homeodomain-interacting protein kinases (Hipks) are serine/threonine kinases involved in regulating transcription factors and developmental processes.

Purpose of the Study:

  • To investigate the role of Hipk in the Hippo tumor suppressor pathway.
  • To determine if Hipk regulates the activity of the transcriptional effector Yorkie (Yki).

Main Methods:

  • Investigated Hipk's effect on Yki stability and subcellular localization.
  • Utilized knockdown experiments to assess Hipk's role in Yki-mediated overgrowth and gene expression.
  • Performed in vivo analyses to examine Hipk's kinase-dependent regulation of Yki.

Main Results:

  • Hipk is required for promoting Yki activity.
  • Hipk does not affect Yki stability or its subcellular localization.
  • Hipk knockdown suppresses overgrowth and target gene expression induced by hyperactive Yki.
  • Hipk directly phosphorylates Yki in a kinase-dependent manner.

Conclusions:

  • Hipk is a novel positive regulator of Yki activity within the Hippo pathway.
  • This study identifies Hipk as the first kinase demonstrated to positively regulate Yki.
  • Hipk's kinase activity is essential for its regulation of Yki and subsequent control of tissue growth.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...