# Role of Biomechanical Interfaces Created by Focal Adhesion Kinase in Catecholamine Signaling

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $681,144

## Abstract

Pioneering work by our MPI team established biomechanical signals as a critical driver of brown adipose tissue
(BAT) function. We demonstrated a new signaling cascade in interscapular BAT that integrates ß-adrenergic
signaling, PKA activation, Ca2+ release via L-type calcium channels, and myosin light chain kinase 1 (MLCK1)
activation. MLCK1 in turn stimulates force generation by myosin 7 (Myh7, a.k.a. cardiac/skeletal myosin heavy
chain beta) and translocation of YAP and TAZ to the nucleus, leading to greater UCP1 expression and enhanced
thermogenesis. Besides classical BAT, inducible beige adipocytes (BeAT) can also contribute to non-shivering
thermogenesis by forming UCP1-positive cells within white adipose tissue (WAT) depots and are thought to be
major drivers of non-shivering thermogenesis in adult humans. While BA are also activated by ß-adrenergic
signals, we found that BeAT do not express Myh7, raising the question of whether BeAT thermogenesis is driven
by contractile signals or some distinct mechanism. Here, we postulate that biointerfacial and biomechanical
forces regulate b-adrenergic receptor (b-AR) signaling in BeAT to link catecholamine signaling to BeAT
differentiation and induction of thermogenesis via Myh9-driven tension. Further, we propose that extracellular
matrix (ECM) modulates ß-AR signaling by integrating, at the level of FAK, myosin-based intracellular tension
signals with biomechanical extracellular matrix clues and outside-in integrin signaling resulting in spatio-temporal
control of BeAT induction.

## Key facts

- **NIH application ID:** 10998792
- **Project number:** 1R01DK141135-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Sanjay Kumar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $681,144
- **Award type:** 1
- **Project period:** 2024-09-10 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998792

## Citation

> US National Institutes of Health, RePORTER application 10998792, Role of Biomechanical Interfaces Created by Focal Adhesion Kinase in Catecholamine Signaling (1R01DK141135-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10998792. Licensed CC0.

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